TY  - JOUR
AU  - Jadranin, Milka
AU  - Savić, Danica
AU  - Lupšić, Ema
AU  - Podolski-Renić, Ana
AU  - Pešić, Milica
AU  - Tešević, Vele
AU  - Milosavljević, Slobodan M.
AU  - Krstić, Gordana B.
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7540
AB  - Euphorbia seguieriana ssp. seguieriana Necker (ES) and Euphorbia cyparissias (EC) with a habitat in the Deliblato Sands were the subject of this examination. The latexes of these so far insufficiently investigated species of the Euphorbia genus are used in traditional medicine for the treatment of wounds and warts on the skin. To determine their chemical composition, non-targeted screening of the latexes’ chloroform extracts was performed using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry employing an electrospray ionization source (LC-ESI QTOF MS). The analysis of the obtained results showed that the latexes of ES and EC represent rich sources of diterpenes, tentatively identified as jatrophanes, ingenanes, tiglianes, myrsinanes, premyrsinanes, and others. Examination of the anticancer activity of the ES and EC latex extracts showed that both extracts significantly inhibited the growth of the non-small cell lung carcinoma NCI-H460 and glioblastoma U87 cell lines as well as of their corresponding multi-drug resistant (MDR) cell lines, NCI-H460/R and U87-TxR. The obtained results also revealed that the ES and EC extracts inhibited the function of P-glycoprotein (P-gp) in MDR cancer cells, whose overexpression is one of the main mechanisms underlying MDR.
PB  - MDPI
T2  - Plants
T1  - LC-ESI QToF MS Non-Targeted Screening of Latex Extracts of Euphorbia seguieriana ssp. seguieriana Necker and Euphorbia cyparissias and Determination of Their Potential Anticancer Activity
VL  - 12
IS  - 24
SP  - 4181
DO  - 10.3390/plants12244181
ER  - 

@article{
author = "Jadranin, Milka and Savić, Danica and Lupšić, Ema and Podolski-Renić, Ana and Pešić, Milica and Tešević, Vele and Milosavljević, Slobodan M. and Krstić, Gordana B.",
year = "2023",
abstract = "Euphorbia seguieriana ssp. seguieriana Necker (ES) and Euphorbia cyparissias (EC) with a habitat in the Deliblato Sands were the subject of this examination. The latexes of these so far insufficiently investigated species of the Euphorbia genus are used in traditional medicine for the treatment of wounds and warts on the skin. To determine their chemical composition, non-targeted screening of the latexes’ chloroform extracts was performed using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry employing an electrospray ionization source (LC-ESI QTOF MS). The analysis of the obtained results showed that the latexes of ES and EC represent rich sources of diterpenes, tentatively identified as jatrophanes, ingenanes, tiglianes, myrsinanes, premyrsinanes, and others. Examination of the anticancer activity of the ES and EC latex extracts showed that both extracts significantly inhibited the growth of the non-small cell lung carcinoma NCI-H460 and glioblastoma U87 cell lines as well as of their corresponding multi-drug resistant (MDR) cell lines, NCI-H460/R and U87-TxR. The obtained results also revealed that the ES and EC extracts inhibited the function of P-glycoprotein (P-gp) in MDR cancer cells, whose overexpression is one of the main mechanisms underlying MDR.",
publisher = "MDPI",
journal = "Plants",
title = "LC-ESI QToF MS Non-Targeted Screening of Latex Extracts of Euphorbia seguieriana ssp. seguieriana Necker and Euphorbia cyparissias and Determination of Their Potential Anticancer Activity",
volume = "12",
number = "24",
pages = "4181",
doi = "10.3390/plants12244181"
}

Jadranin, M., Savić, D., Lupšić, E., Podolski-Renić, A., Pešić, M., Tešević, V., Milosavljević, S. M.,& Krstić, G. B.. (2023). LC-ESI QToF MS Non-Targeted Screening of Latex Extracts of Euphorbia seguieriana ssp. seguieriana Necker and Euphorbia cyparissias and Determination of Their Potential Anticancer Activity. in Plants
MDPI., 12(24), 4181.
https://doi.org/10.3390/plants12244181

Jadranin M, Savić D, Lupšić E, Podolski-Renić A, Pešić M, Tešević V, Milosavljević SM, Krstić GB. LC-ESI QToF MS Non-Targeted Screening of Latex Extracts of Euphorbia seguieriana ssp. seguieriana Necker and Euphorbia cyparissias and Determination of Their Potential Anticancer Activity. in Plants. 2023;12(24):4181.
doi:10.3390/plants12244181 .

Jadranin, Milka, Savić, Danica, Lupšić, Ema, Podolski-Renić, Ana, Pešić, Milica, Tešević, Vele, Milosavljević, Slobodan M., Krstić, Gordana B., "LC-ESI QToF MS Non-Targeted Screening of Latex Extracts of Euphorbia seguieriana ssp. seguieriana Necker and Euphorbia cyparissias and Determination of Their Potential Anticancer Activity" in Plants, 12, no. 24 (2023):4181,
https://doi.org/10.3390/plants12244181 . .

TY  - CONF
AU  - Stepanović, Ana
AU  - Lupšić, Ema
AU  - Dinić, Jelena
AU  - Podolski-Renić, Ana
AU  - Pajović, Milica
AU  - Jovanović Stojanov, Sofija
AU  - Dragoj, Miodrag
AU  - Terzić Jovanović, Nataša
AU  - Opsenica, Igor
AU  - Pešić, Milica
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/6678
AB  - Background: Doxorubicin (DOX) has been very effective against glioblastoma invitro. Its application in vivo is hampered because it cannot pass the blood–brainbarrier (BBB). Significant research efforts are invested to overcome this limitation.Sclareol (SC) is an aromatic compound naturally found in clary sage. Thecombination of SC and DOX showed promising effects in different tumor types invitro and in vivo. Therefore, we tested their combination and innovative hybridmolecules (SC:DOX) on glioblastoma cells with the expression of P-glycoprotein, amajor component of BBB and cancer multidrug resistance marker. Methods:Cytotoxicity and selectivity towards glioblastoma cells of SC, DOX, theircombination, and SC:DOX were examined by MTT assay. The effect of SC on DOXaccumulation was determined by flow cytometry. We also studied SC:DOXaccumulation, cellular uptake, localization imaging, and DNA damage induction.Results: The effects of simultaneous SC and DOX treatments demonstrated theconsiderable potential of SC to reverse DOX resistance in glioblastoma cells andincrease DOX accumulation. SC:DOX hybrids, named CON1 and CON2 were lesscytotoxic than DOX, but with reduced resistance and increased selectivity towardsglioblastoma cells. Cellular uptake of CON1 and CON2 was increased in glioblastomacells compared to DOX. Perinuclear localization of CON1 and CON2 vs. nuclearlocalization of DOX as well as no DNA damaging effects suggest a differentmechanism of action for SC:DOX. Conclusion: The combination of SC and DOX, andtheir innovative hybrids, could be considered a promising strategy that can overcomethe limitations of DOX application in glioblastoma.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts - 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - New anti-glioblastoma strategy with natural compounds sclareol and doxorubicin
SP  - 71
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5905
ER  - 

@conference{
author = "Stepanović, Ana and Lupšić, Ema and Dinić, Jelena and Podolski-Renić, Ana and Pajović, Milica and Jovanović Stojanov, Sofija and Dragoj, Miodrag and Terzić Jovanović, Nataša and Opsenica, Igor and Pešić, Milica",
year = "2023",
abstract = "Background: Doxorubicin (DOX) has been very effective against glioblastoma invitro. Its application in vivo is hampered because it cannot pass the blood–brainbarrier (BBB). Significant research efforts are invested to overcome this limitation.Sclareol (SC) is an aromatic compound naturally found in clary sage. Thecombination of SC and DOX showed promising effects in different tumor types invitro and in vivo. Therefore, we tested their combination and innovative hybridmolecules (SC:DOX) on glioblastoma cells with the expression of P-glycoprotein, amajor component of BBB and cancer multidrug resistance marker. Methods:Cytotoxicity and selectivity towards glioblastoma cells of SC, DOX, theircombination, and SC:DOX were examined by MTT assay. The effect of SC on DOXaccumulation was determined by flow cytometry. We also studied SC:DOXaccumulation, cellular uptake, localization imaging, and DNA damage induction.Results: The effects of simultaneous SC and DOX treatments demonstrated theconsiderable potential of SC to reverse DOX resistance in glioblastoma cells andincrease DOX accumulation. SC:DOX hybrids, named CON1 and CON2 were lesscytotoxic than DOX, but with reduced resistance and increased selectivity towardsglioblastoma cells. Cellular uptake of CON1 and CON2 was increased in glioblastomacells compared to DOX. Perinuclear localization of CON1 and CON2 vs. nuclearlocalization of DOX as well as no DNA damaging effects suggest a differentmechanism of action for SC:DOX. Conclusion: The combination of SC and DOX, andtheir innovative hybrids, could be considered a promising strategy that can overcomethe limitations of DOX application in glioblastoma.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts - 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "New anti-glioblastoma strategy with natural compounds sclareol and doxorubicin",
pages = "71",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5905"
}

Stepanović, A., Lupšić, E., Dinić, J., Podolski-Renić, A., Pajović, M., Jovanović Stojanov, S., Dragoj, M., Terzić Jovanović, N., Opsenica, I.,& Pešić, M.. (2023). New anti-glioblastoma strategy with natural compounds sclareol and doxorubicin. in Book of abstracts - 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 71.
https://hdl.handle.net/21.15107/rcub_ibiss_5905

Stepanović A, Lupšić E, Dinić J, Podolski-Renić A, Pajović M, Jovanović Stojanov S, Dragoj M, Terzić Jovanović N, Opsenica I, Pešić M. New anti-glioblastoma strategy with natural compounds sclareol and doxorubicin. in Book of abstracts - 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:71.
https://hdl.handle.net/21.15107/rcub_ibiss_5905 .

Stepanović, Ana, Lupšić, Ema, Dinić, Jelena, Podolski-Renić, Ana, Pajović, Milica, Jovanović Stojanov, Sofija, Dragoj, Miodrag, Terzić Jovanović, Nataša, Opsenica, Igor, Pešić, Milica, "New anti-glioblastoma strategy with natural compounds sclareol and doxorubicin" in Book of abstracts - 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):71,
https://hdl.handle.net/21.15107/rcub_ibiss_5905 .

TY  - CONF
AU  - Jadranin, Milka
AU  - Krstić, Gordana
AU  - Savić, Danica
AU  - Novaković, Miroslav
AU  - Lekić, Stefan
AU  - Tešević, Vele
AU  - Pešić, Milica
AU  - Podolski-Renić, Ana
AU  - Lupšić, Ema
AU  - Milosavljević, Slobodan
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7270
AB  - Euphorbia cyparissias L. (cypress spurge) is one of the many species of the genus Euphorbia. Like other plant species of the genus, E. cyparissias is a source of biologically active compounds [1, 2]. The aim of this research was to profile the chloroform-methanol latex extract and detect the type of secondary metabolites of Serbian E. cyparissias, collected in Deliblato Sand 
(Serbia) in May 2022, using liquid chromatography – electrospray ionisation mass spectrometry. Based on the obtained results, terpene derivatives have been found as the most abundant in the latex extract, mainly diterpenes (jatrophanes and ingenanes) and triterpenes. Also, the anticancer activ ity of the latex extract on the cell lines NCI-H460, NCI-H460/R, U87, U87/
TxR and MRC-5, as well as the ability to inhibit P-gp, were examined. Latex extract exhibited anticancer activity against all tested cell lines, and also 
proved to be a strong P-gp inhibitor. The obtained results are in accordance with the literature data because jatrophanes are well-known strong P-gp 
inhibitors [3]. These preliminary results indicate that this plant material is a rich source of biologically active compounds and detailed phytochemical research of E. cyparissias is further planned.
PB  - International Conference on Natural Products Utilization - ICNPU2023
C3  - Book of Abstracts - The 5th International Conference on Natural Products Utilization: from Plants to Pharmacy Shelf (ICNPU-2023), 30 May–02 June 2023, Sts. Constantine and Helena - Varna, Bulgaria
T1  - Analysis of terpenoids from the latex of Euphorbia cyparissias by liquid chromatography-electrospray ionization mass spectrometry
SP  - 184
EP  - 185
UR  - https://hdl.handle.net/21.15107/rcub_cer_7270
ER  - 

@conference{
author = "Jadranin, Milka and Krstić, Gordana and Savić, Danica and Novaković, Miroslav and Lekić, Stefan and Tešević, Vele and Pešić, Milica and Podolski-Renić, Ana and Lupšić, Ema and Milosavljević, Slobodan",
year = "2023",
abstract = "Euphorbia cyparissias L. (cypress spurge) is one of the many species of the genus Euphorbia. Like other plant species of the genus, E. cyparissias is a source of biologically active compounds [1, 2]. The aim of this research was to profile the chloroform-methanol latex extract and detect the type of secondary metabolites of Serbian E. cyparissias, collected in Deliblato Sand 
(Serbia) in May 2022, using liquid chromatography – electrospray ionisation mass spectrometry. Based on the obtained results, terpene derivatives have been found as the most abundant in the latex extract, mainly diterpenes (jatrophanes and ingenanes) and triterpenes. Also, the anticancer activ ity of the latex extract on the cell lines NCI-H460, NCI-H460/R, U87, U87/
TxR and MRC-5, as well as the ability to inhibit P-gp, were examined. Latex extract exhibited anticancer activity against all tested cell lines, and also 
proved to be a strong P-gp inhibitor. The obtained results are in accordance with the literature data because jatrophanes are well-known strong P-gp 
inhibitors [3]. These preliminary results indicate that this plant material is a rich source of biologically active compounds and detailed phytochemical research of E. cyparissias is further planned.",
publisher = "International Conference on Natural Products Utilization - ICNPU2023",
journal = "Book of Abstracts - The 5th International Conference on Natural Products Utilization: from Plants to Pharmacy Shelf (ICNPU-2023), 30 May–02 June 2023, Sts. Constantine and Helena - Varna, Bulgaria",
title = "Analysis of terpenoids from the latex of Euphorbia cyparissias by liquid chromatography-electrospray ionization mass spectrometry",
pages = "184-185",
url = "https://hdl.handle.net/21.15107/rcub_cer_7270"
}

Jadranin, M., Krstić, G., Savić, D., Novaković, M., Lekić, S., Tešević, V., Pešić, M., Podolski-Renić, A., Lupšić, E.,& Milosavljević, S.. (2023). Analysis of terpenoids from the latex of Euphorbia cyparissias by liquid chromatography-electrospray ionization mass spectrometry. in Book of Abstracts - The 5th International Conference on Natural Products Utilization: from Plants to Pharmacy Shelf (ICNPU-2023), 30 May–02 June 2023, Sts. Constantine and Helena - Varna, Bulgaria
International Conference on Natural Products Utilization - ICNPU2023., 184-185.
https://hdl.handle.net/21.15107/rcub_cer_7270

Jadranin M, Krstić G, Savić D, Novaković M, Lekić S, Tešević V, Pešić M, Podolski-Renić A, Lupšić E, Milosavljević S. Analysis of terpenoids from the latex of Euphorbia cyparissias by liquid chromatography-electrospray ionization mass spectrometry. in Book of Abstracts - The 5th International Conference on Natural Products Utilization: from Plants to Pharmacy Shelf (ICNPU-2023), 30 May–02 June 2023, Sts. Constantine and Helena - Varna, Bulgaria. 2023;:184-185.
https://hdl.handle.net/21.15107/rcub_cer_7270 .

Jadranin, Milka, Krstić, Gordana, Savić, Danica, Novaković, Miroslav, Lekić, Stefan, Tešević, Vele, Pešić, Milica, Podolski-Renić, Ana, Lupšić, Ema, Milosavljević, Slobodan, "Analysis of terpenoids from the latex of Euphorbia cyparissias by liquid chromatography-electrospray ionization mass spectrometry" in Book of Abstracts - The 5th International Conference on Natural Products Utilization: from Plants to Pharmacy Shelf (ICNPU-2023), 30 May–02 June 2023, Sts. Constantine and Helena - Varna, Bulgaria (2023):184-185,
https://hdl.handle.net/21.15107/rcub_cer_7270 .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Novaković, Miroslav
AU  - Podolski-Renic, Ana
AU  - Vajs, Vlatka
AU  - Tešević, Vele
AU  - Isaković, Aleksandra
AU  - Pešić, Milica
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4162
AB  - Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 30 and 300-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 30 and 300-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells.
PB  - Elsevier
T2  - Chemico-Biological Interactions
T1  - Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells
VL  - 249
SP  - 36
EP  - 45
DO  - 10.1016/j.cbi.2016.02.019
ER  - 

@article{
author = "Dinić, Jelena and Novaković, Miroslav and Podolski-Renic, Ana and Vajs, Vlatka and Tešević, Vele and Isaković, Aleksandra and Pešić, Milica",
year = "2016",
abstract = "Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 30 and 300-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 30 and 300-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells.",
publisher = "Elsevier",
journal = "Chemico-Biological Interactions",
title = "Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells",
volume = "249",
pages = "36-45",
doi = "10.1016/j.cbi.2016.02.019"
}

Dinić, J., Novaković, M., Podolski-Renic, A., Vajs, V., Tešević, V., Isaković, A.,& Pešić, M.. (2016). Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells. in Chemico-Biological Interactions
Elsevier., 249, 36-45.
https://doi.org/10.1016/j.cbi.2016.02.019

Dinić J, Novaković M, Podolski-Renic A, Vajs V, Tešević V, Isaković A, Pešić M. Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells. in Chemico-Biological Interactions. 2016;249:36-45.
doi:10.1016/j.cbi.2016.02.019 .

Dinić, Jelena, Novaković, Miroslav, Podolski-Renic, Ana, Vajs, Vlatka, Tešević, Vele, Isaković, Aleksandra, Pešić, Milica, "Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells" in Chemico-Biological Interactions, 249 (2016):36-45,
https://doi.org/10.1016/j.cbi.2016.02.019 . .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Novaković, Miroslav
AU  - Podolski-Renic, Ana
AU  - Vajs, Vlatka
AU  - Tešević, Vele
AU  - Isaković, Aleksandra
AU  - Pešić, Milica
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1970
AB  - Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 30 and 300-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 30 and 300-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells.
PB  - Elsevier Ireland Ltd, Clare
T2  - Chemico-Biological Interactions
T1  - Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells
VL  - 249
SP  - 36
EP  - 45
DO  - 10.1016/j.cbi.2016.02.019
ER  - 

@article{
author = "Dinić, Jelena and Novaković, Miroslav and Podolski-Renic, Ana and Vajs, Vlatka and Tešević, Vele and Isaković, Aleksandra and Pešić, Milica",
year = "2016",
abstract = "Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 30 and 300-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 30 and 300-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells.",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Chemico-Biological Interactions",
title = "Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells",
volume = "249",
pages = "36-45",
doi = "10.1016/j.cbi.2016.02.019"
}

Dinić, J., Novaković, M., Podolski-Renic, A., Vajs, V., Tešević, V., Isaković, A.,& Pešić, M.. (2016). Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells. in Chemico-Biological Interactions
Elsevier Ireland Ltd, Clare., 249, 36-45.
https://doi.org/10.1016/j.cbi.2016.02.019

Dinić J, Novaković M, Podolski-Renic A, Vajs V, Tešević V, Isaković A, Pešić M. Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells. in Chemico-Biological Interactions. 2016;249:36-45.
doi:10.1016/j.cbi.2016.02.019 .

Dinić, Jelena, Novaković, Miroslav, Podolski-Renic, Ana, Vajs, Vlatka, Tešević, Vele, Isaković, Aleksandra, Pešić, Milica, "Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells" in Chemico-Biological Interactions, 249 (2016):36-45,
https://doi.org/10.1016/j.cbi.2016.02.019 . .

TY  - JOUR
AU  - Novaković, Miroslav
AU  - Pešić, Milica
AU  - Trifunović, Snežana
AU  - Vučković, Ivan
AU  - Todorović, Nina
AU  - Podolski-Renic, Ana
AU  - Dinić, Jelena
AU  - Stojkovic, Sonja
AU  - Tešević, Vele
AU  - Vajs, Vlatka
AU  - Milosavljević, Slobodan
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1549
AB  - An extended study of minor diarylheptanoids from the bark of black alder has resulted in the isolation of twenty diarylheptanoids, ten of which have not previously been reported (14-18, 20-24). The structures and configurations of all compounds were elucidated by NMR, HRESIMS, UV, IR, and CD. The anti-cancer potency of twenty diarylheptanoids and four previously isolated compounds (7, 10, 12, 13) was investigated in human non-small cell lung carcinoma cell lines (sensitive and multi-drug resistant variants) as well as in normal human keratinocytes. Diarylheptanoids with a p-coumaroyl group, 14 and 18, platyphylloside (1), platyphyllonol-5-O-beta-D-xylopyranoside (2), alnuside B (4) and hirsutenone (9) exhibited strong anti-cancer activity, considerably higher than diarylheptanoid curcumin, which served as a positive control. Compounds 4, 9, 14, and 18 displayed significant selectivity towards the cancer cells. Structure/activity analysis of twenty-four closely related diarylheptanoids revealed a high dependence of cytotoxic action on the presence of a carbonyl group at C-3. Substitution of a heptane chain on C-5 and a number of hydroxyl groups in the aromatic rings also emerged as a significant structural feature that influenced their cytotoxic potential.
PB  - Oxford : Pergamon-Elsevier Science Ltd
T2  - Phytochemistry
T1  - Diarylheptanoids from the bark of black alder inhibit the growth of sensitive and multi-drug resistant non-small cell lung carcinoma cells
VL  - 97
SP  - 46
EP  - 54
DO  - 10.1016/j.phytochem.2013.11.001
ER  - 

@article{
author = "Novaković, Miroslav and Pešić, Milica and Trifunović, Snežana and Vučković, Ivan and Todorović, Nina and Podolski-Renic, Ana and Dinić, Jelena and Stojkovic, Sonja and Tešević, Vele and Vajs, Vlatka and Milosavljević, Slobodan",
year = "2014",
abstract = "An extended study of minor diarylheptanoids from the bark of black alder has resulted in the isolation of twenty diarylheptanoids, ten of which have not previously been reported (14-18, 20-24). The structures and configurations of all compounds were elucidated by NMR, HRESIMS, UV, IR, and CD. The anti-cancer potency of twenty diarylheptanoids and four previously isolated compounds (7, 10, 12, 13) was investigated in human non-small cell lung carcinoma cell lines (sensitive and multi-drug resistant variants) as well as in normal human keratinocytes. Diarylheptanoids with a p-coumaroyl group, 14 and 18, platyphylloside (1), platyphyllonol-5-O-beta-D-xylopyranoside (2), alnuside B (4) and hirsutenone (9) exhibited strong anti-cancer activity, considerably higher than diarylheptanoid curcumin, which served as a positive control. Compounds 4, 9, 14, and 18 displayed significant selectivity towards the cancer cells. Structure/activity analysis of twenty-four closely related diarylheptanoids revealed a high dependence of cytotoxic action on the presence of a carbonyl group at C-3. Substitution of a heptane chain on C-5 and a number of hydroxyl groups in the aromatic rings also emerged as a significant structural feature that influenced their cytotoxic potential.",
publisher = "Oxford : Pergamon-Elsevier Science Ltd",
journal = "Phytochemistry",
title = "Diarylheptanoids from the bark of black alder inhibit the growth of sensitive and multi-drug resistant non-small cell lung carcinoma cells",
volume = "97",
pages = "46-54",
doi = "10.1016/j.phytochem.2013.11.001"
}

Novaković, M., Pešić, M., Trifunović, S., Vučković, I., Todorović, N., Podolski-Renic, A., Dinić, J., Stojkovic, S., Tešević, V., Vajs, V.,& Milosavljević, S.. (2014). Diarylheptanoids from the bark of black alder inhibit the growth of sensitive and multi-drug resistant non-small cell lung carcinoma cells. in Phytochemistry
Oxford : Pergamon-Elsevier Science Ltd., 97, 46-54.
https://doi.org/10.1016/j.phytochem.2013.11.001

Novaković M, Pešić M, Trifunović S, Vučković I, Todorović N, Podolski-Renic A, Dinić J, Stojkovic S, Tešević V, Vajs V, Milosavljević S. Diarylheptanoids from the bark of black alder inhibit the growth of sensitive and multi-drug resistant non-small cell lung carcinoma cells. in Phytochemistry. 2014;97:46-54.
doi:10.1016/j.phytochem.2013.11.001 .

Novaković, Miroslav, Pešić, Milica, Trifunović, Snežana, Vučković, Ivan, Todorović, Nina, Podolski-Renic, Ana, Dinić, Jelena, Stojkovic, Sonja, Tešević, Vele, Vajs, Vlatka, Milosavljević, Slobodan, "Diarylheptanoids from the bark of black alder inhibit the growth of sensitive and multi-drug resistant non-small cell lung carcinoma cells" in Phytochemistry, 97 (2014):46-54,
https://doi.org/10.1016/j.phytochem.2013.11.001 . .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Novaković, Miroslav
AU  - Podolski-Renic, Ana
AU  - Stojkovic, Sonja
AU  - Mandić, Boris
AU  - Tešević, Vele
AU  - Vajs, Vlatka
AU  - Isaković, Aleksandra
AU  - Pešić, Milica
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1434
AB  - Diarylheptanoids belong to polyphenols, a group of plant secondary metabolites with multiple biological properties. Many of them display antioxidative, cytotoxic, or anticancer actions and are increasingly recognized as potential therapeutic agents. The aim of this study was to evaluate antioxidant and cytoprotective activity of two diarylheptanoids: platyphylloside 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-beta-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-beta-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2), both isolated from the bark of black alder (Alnus glutinosa). To that end, we have employed a cancer cell line (NCI-H460), normal human keratinocytes (HaCaT), and peripheral blood mononuclear cells. The effects on cell growth were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Cell death was examined by annexin V/propidium iodide staining on a flow cytometer. Reactive oxygen species production was examined by dihydroethidium staining. Mitochondrial structure and doxorubicin localization were visualized by fluorescent microscopy. Gene expression of manganese superoxide dismutase and hypoxia-inducible factor-1 alpha was determined by reverse transcription polymerase chain reaction. Diarylheptanoids antagonized the effects of either doxorubicin or cisplatin, significantly increasing their IC50 values in normal cells. Diarylheptanoid 1 induced the retention of doxorubicin in cytoplasm and reduced mitochondrial fragmentation associated with doxorubicin application. Diarylheptanoid 2 reduced the reactive oxygen species production induced by cisplatin. Both compounds increased the messenger ribonucleic acid expression of enzymes involved in reactive oxygen species elimination (manganese superoxide dismutase and hypoxia-inducible factor-1 alpha). These results indicate that neutralization of reactive oxygen species is an important mechanism of diarylheptanoid action, although these compounds exert a considerable anticancer effect. Therefore, these compounds may serve as protectors of normal cells during chemotherapy without significantly diminishing the effect of the applied chemotherapeutic.
PB  - Georg Thieme Verlag Kg, Stuttgart
T2  - Planta Medica
T1  - Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus glutinosa) and Their Interaction with Anticancer Drugs
VL  - 80
IS  - 13
SP  - 1088
EP  - 1096
DO  - 10.1055/s-0034-1382993
ER  - 

@article{
author = "Dinić, Jelena and Novaković, Miroslav and Podolski-Renic, Ana and Stojkovic, Sonja and Mandić, Boris and Tešević, Vele and Vajs, Vlatka and Isaković, Aleksandra and Pešić, Milica",
year = "2014",
abstract = "Diarylheptanoids belong to polyphenols, a group of plant secondary metabolites with multiple biological properties. Many of them display antioxidative, cytotoxic, or anticancer actions and are increasingly recognized as potential therapeutic agents. The aim of this study was to evaluate antioxidant and cytoprotective activity of two diarylheptanoids: platyphylloside 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-beta-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-beta-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2), both isolated from the bark of black alder (Alnus glutinosa). To that end, we have employed a cancer cell line (NCI-H460), normal human keratinocytes (HaCaT), and peripheral blood mononuclear cells. The effects on cell growth were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Cell death was examined by annexin V/propidium iodide staining on a flow cytometer. Reactive oxygen species production was examined by dihydroethidium staining. Mitochondrial structure and doxorubicin localization were visualized by fluorescent microscopy. Gene expression of manganese superoxide dismutase and hypoxia-inducible factor-1 alpha was determined by reverse transcription polymerase chain reaction. Diarylheptanoids antagonized the effects of either doxorubicin or cisplatin, significantly increasing their IC50 values in normal cells. Diarylheptanoid 1 induced the retention of doxorubicin in cytoplasm and reduced mitochondrial fragmentation associated with doxorubicin application. Diarylheptanoid 2 reduced the reactive oxygen species production induced by cisplatin. Both compounds increased the messenger ribonucleic acid expression of enzymes involved in reactive oxygen species elimination (manganese superoxide dismutase and hypoxia-inducible factor-1 alpha). These results indicate that neutralization of reactive oxygen species is an important mechanism of diarylheptanoid action, although these compounds exert a considerable anticancer effect. Therefore, these compounds may serve as protectors of normal cells during chemotherapy without significantly diminishing the effect of the applied chemotherapeutic.",
publisher = "Georg Thieme Verlag Kg, Stuttgart",
journal = "Planta Medica",
title = "Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus glutinosa) and Their Interaction with Anticancer Drugs",
volume = "80",
number = "13",
pages = "1088-1096",
doi = "10.1055/s-0034-1382993"
}

Dinić, J., Novaković, M., Podolski-Renic, A., Stojkovic, S., Mandić, B., Tešević, V., Vajs, V., Isaković, A.,& Pešić, M.. (2014). Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus glutinosa) and Their Interaction with Anticancer Drugs. in Planta Medica
Georg Thieme Verlag Kg, Stuttgart., 80(13), 1088-1096.
https://doi.org/10.1055/s-0034-1382993

Dinić J, Novaković M, Podolski-Renic A, Stojkovic S, Mandić B, Tešević V, Vajs V, Isaković A, Pešić M. Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus glutinosa) and Their Interaction with Anticancer Drugs. in Planta Medica. 2014;80(13):1088-1096.
doi:10.1055/s-0034-1382993 .

Dinić, Jelena, Novaković, Miroslav, Podolski-Renic, Ana, Stojkovic, Sonja, Mandić, Boris, Tešević, Vele, Vajs, Vlatka, Isaković, Aleksandra, Pešić, Milica, "Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus glutinosa) and Their Interaction with Anticancer Drugs" in Planta Medica, 80, no. 13 (2014):1088-1096,
https://doi.org/10.1055/s-0034-1382993 . .

TY  - JOUR
AU  - Aljančić, Ivana
AU  - Vučković, Ivan
AU  - Jadranin, Milka
AU  - Pešić, Milica
AU  - Đorđević, Iris
AU  - Podolski-Renic, Ana
AU  - Stojkovic, Sonja
AU  - Menković, Nebojša
AU  - Vajs, Vlatka
AU  - Milosavljević, Slobodan
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1542
AB  - Dimers tomoroside A (1) and tomoroside B (2) of the co-occuring known chalcone monomer (3), along with the seven known flavonoid glucosides (4-10), were isolated from the aerial parts of Helichrysum zivojinii Cernjavski & Soska. The structures of the isolated compounds were elucidated by spectroscopic techniques. Compound 1 inhibited topo Ha and hif-1 alpha expression and stimulated doxorubicin anticancer effect, while 2 increased the expression of hif-1 alpha a, probably acting as antioxidant and redox status modulator. Notably, 2 synergized with Tipifarnib showing potential to improve the action of this new chemotherapeutic involved in the modulation of mitogene activated protein (MAP) kinase signaling pathway.
PB  - Oxford : Pergamon-Elsevier Science Ltd
T2  - Phytochemistry
T1  - Two structurally distinct chalcone dimers from Helichrysum zivojinii and their activities in cancer cell lines
VL  - 98
SP  - 190
EP  - 196
DO  - 10.1016/j.phytochem.2013.11.025
ER  - 

@article{
author = "Aljančić, Ivana and Vučković, Ivan and Jadranin, Milka and Pešić, Milica and Đorđević, Iris and Podolski-Renic, Ana and Stojkovic, Sonja and Menković, Nebojša and Vajs, Vlatka and Milosavljević, Slobodan",
year = "2014",
abstract = "Dimers tomoroside A (1) and tomoroside B (2) of the co-occuring known chalcone monomer (3), along with the seven known flavonoid glucosides (4-10), were isolated from the aerial parts of Helichrysum zivojinii Cernjavski & Soska. The structures of the isolated compounds were elucidated by spectroscopic techniques. Compound 1 inhibited topo Ha and hif-1 alpha expression and stimulated doxorubicin anticancer effect, while 2 increased the expression of hif-1 alpha a, probably acting as antioxidant and redox status modulator. Notably, 2 synergized with Tipifarnib showing potential to improve the action of this new chemotherapeutic involved in the modulation of mitogene activated protein (MAP) kinase signaling pathway.",
publisher = "Oxford : Pergamon-Elsevier Science Ltd",
journal = "Phytochemistry",
title = "Two structurally distinct chalcone dimers from Helichrysum zivojinii and their activities in cancer cell lines",
volume = "98",
pages = "190-196",
doi = "10.1016/j.phytochem.2013.11.025"
}

Aljančić, I., Vučković, I., Jadranin, M., Pešić, M., Đorđević, I., Podolski-Renic, A., Stojkovic, S., Menković, N., Vajs, V.,& Milosavljević, S.. (2014). Two structurally distinct chalcone dimers from Helichrysum zivojinii and their activities in cancer cell lines. in Phytochemistry
Oxford : Pergamon-Elsevier Science Ltd., 98, 190-196.
https://doi.org/10.1016/j.phytochem.2013.11.025

Aljančić I, Vučković I, Jadranin M, Pešić M, Đorđević I, Podolski-Renic A, Stojkovic S, Menković N, Vajs V, Milosavljević S. Two structurally distinct chalcone dimers from Helichrysum zivojinii and their activities in cancer cell lines. in Phytochemistry. 2014;98:190-196.
doi:10.1016/j.phytochem.2013.11.025 .

Aljančić, Ivana, Vučković, Ivan, Jadranin, Milka, Pešić, Milica, Đorđević, Iris, Podolski-Renic, Ana, Stojkovic, Sonja, Menković, Nebojša, Vajs, Vlatka, Milosavljević, Slobodan, "Two structurally distinct chalcone dimers from Helichrysum zivojinii and their activities in cancer cell lines" in Phytochemistry, 98 (2014):190-196,
https://doi.org/10.1016/j.phytochem.2013.11.025 . .

TY  - JOUR
AU  - Jadranin, Milka
AU  - Pešić, Milica
AU  - Aljančić, Ivana
AU  - Milosavljević, Slobodan
AU  - Todorović, Nina
AU  - Podolski-Renic, Ana
AU  - Bankovic, Jasna
AU  - Tanic, Nikola
AU  - Markovic, Ivanka
AU  - Vajs, Vlatka
AU  - Tešević, Vele
PY  - 2013
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1278
AB  - Thirteen jatrophane diterpenoids (1-10, 13-15), three previously isolated (11, 12, 16) and a known tigliane (17) were isolated from the latex of Euphorbia dendroides. The structures and relative configurations of compounds were elucidated by spectroscopic techniques. The P-glycoprotein (P-gp) inhibiting activities of the representative set of jatrophanes (1-6 and 11-16) have been assessed. Jatrophanes 2 and 5 demonstrated the most powerful inhibition of P-gp, higher than R(+)-verapamil and tariquidar in colorectal multi-drug resistant (MDR) cells (DLD1-TxR).
PB  - Oxford : Pergamon-Elsevier Science Ltd
T2  - Phytochemistry
T1  - Jatrophane diterpenoids from the latex of Euphorbia dendroides and their anti-P-glycoprotein activity in human multi-drug resistant cancer cell lines
VL  - 86
SP  - 208
EP  - 217
DO  - 10.1016/j.phytochem.2012.09.003
ER  - 

@article{
author = "Jadranin, Milka and Pešić, Milica and Aljančić, Ivana and Milosavljević, Slobodan and Todorović, Nina and Podolski-Renic, Ana and Bankovic, Jasna and Tanic, Nikola and Markovic, Ivanka and Vajs, Vlatka and Tešević, Vele",
year = "2013",
abstract = "Thirteen jatrophane diterpenoids (1-10, 13-15), three previously isolated (11, 12, 16) and a known tigliane (17) were isolated from the latex of Euphorbia dendroides. The structures and relative configurations of compounds were elucidated by spectroscopic techniques. The P-glycoprotein (P-gp) inhibiting activities of the representative set of jatrophanes (1-6 and 11-16) have been assessed. Jatrophanes 2 and 5 demonstrated the most powerful inhibition of P-gp, higher than R(+)-verapamil and tariquidar in colorectal multi-drug resistant (MDR) cells (DLD1-TxR).",
publisher = "Oxford : Pergamon-Elsevier Science Ltd",
journal = "Phytochemistry",
title = "Jatrophane diterpenoids from the latex of Euphorbia dendroides and their anti-P-glycoprotein activity in human multi-drug resistant cancer cell lines",
volume = "86",
pages = "208-217",
doi = "10.1016/j.phytochem.2012.09.003"
}

Jadranin, M., Pešić, M., Aljančić, I., Milosavljević, S., Todorović, N., Podolski-Renic, A., Bankovic, J., Tanic, N., Markovic, I., Vajs, V.,& Tešević, V.. (2013). Jatrophane diterpenoids from the latex of Euphorbia dendroides and their anti-P-glycoprotein activity in human multi-drug resistant cancer cell lines. in Phytochemistry
Oxford : Pergamon-Elsevier Science Ltd., 86, 208-217.
https://doi.org/10.1016/j.phytochem.2012.09.003

Jadranin M, Pešić M, Aljančić I, Milosavljević S, Todorović N, Podolski-Renic A, Bankovic J, Tanic N, Markovic I, Vajs V, Tešević V. Jatrophane diterpenoids from the latex of Euphorbia dendroides and their anti-P-glycoprotein activity in human multi-drug resistant cancer cell lines. in Phytochemistry. 2013;86:208-217.
doi:10.1016/j.phytochem.2012.09.003 .

Jadranin, Milka, Pešić, Milica, Aljančić, Ivana, Milosavljević, Slobodan, Todorović, Nina, Podolski-Renic, Ana, Bankovic, Jasna, Tanic, Nikola, Markovic, Ivanka, Vajs, Vlatka, Tešević, Vele, "Jatrophane diterpenoids from the latex of Euphorbia dendroides and their anti-P-glycoprotein activity in human multi-drug resistant cancer cell lines" in Phytochemistry, 86 (2013):208-217,
https://doi.org/10.1016/j.phytochem.2012.09.003 . .

TY  - JOUR
AU  - Podolski-Renic, Ana
AU  - Jadranin, Milka
AU  - Stankovic, Tijana
AU  - Bankovic, Jasna
AU  - Stojkovic, Sonja
AU  - Chiourea, Maria
AU  - Aljančić, Ivana
AU  - Vajs, Vlatka
AU  - Tešević, Vele
AU  - Ruzdijic, Sabera
AU  - Gagos, Sarantis
AU  - Tanic, Nikola
AU  - Pešić, Milica
PY  - 2013
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1176
AB  - Multi-drug resistance (MDR) is a major obstacle to successful cancer treatment. Therefore, in vitro models are necessary for the investigation of the phenotypic changes provoked by cytotoxic agents and more importantly for preclinical testing of new anticancer drugs. We analyzed chromosomal, numerical, and structural changes after development of MDR, alterations in p53 and PTEN, single nucleotide polymorphisms (SNPs) in the mdr1 gene and corresponding protein expression of P-glycoprotein (P-gp) in three human MDR cancer cell lines: non-small cell lung carcinoma NCI-H460/R, colorectal carcinoma DLD1-TxR, and glioma U87-TxR. In addition, we explored how these molecular and phenotypic alterations influence the anticancer effect of new drugs. Cytogenetic analysis showed polyploidy reduction after development of MDR in U87-TxR. Losses of 6q in all resistant cancer cell lines and inactivation of p53 in U87-TxR and PTEN in DLD1-TxR were also revealed. Overexpression of P-gp was observed in all MDR cancer cell lines. We evaluated the anticancer activities and MDR reversal potential of Akt inhibitor GSK690693, Ras inhibitor Tipifarnib, and two P-gp inhibitors (jatrophane diterpenoids). Their effects vary due to the cell-type differences, existence of MDR phenotype, presence of mdr1 SNP, and tumor suppressors' alterations. Tipifarnib and jatrophane diterpenoids significantly sensitized MDR cancer cells to paclitaxel. In conclusion, investigated MDR cancer cells obtained new molecular and cytogenetic characteristics that may serve as potential clinical prognostic markers. In addition, these MDR cancer cell lines present a valuable model for preclinical evaluation of new anticancer agents.
PB  - Springer, New York
T2  - Cancer Chemotherapy and Pharmacology
T1  - Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing
VL  - 72
IS  - 3
SP  - 683
EP  - 697
DO  - 10.1007/s00280-013-2247-1
ER  - 

@article{
author = "Podolski-Renic, Ana and Jadranin, Milka and Stankovic, Tijana and Bankovic, Jasna and Stojkovic, Sonja and Chiourea, Maria and Aljančić, Ivana and Vajs, Vlatka and Tešević, Vele and Ruzdijic, Sabera and Gagos, Sarantis and Tanic, Nikola and Pešić, Milica",
year = "2013",
abstract = "Multi-drug resistance (MDR) is a major obstacle to successful cancer treatment. Therefore, in vitro models are necessary for the investigation of the phenotypic changes provoked by cytotoxic agents and more importantly for preclinical testing of new anticancer drugs. We analyzed chromosomal, numerical, and structural changes after development of MDR, alterations in p53 and PTEN, single nucleotide polymorphisms (SNPs) in the mdr1 gene and corresponding protein expression of P-glycoprotein (P-gp) in three human MDR cancer cell lines: non-small cell lung carcinoma NCI-H460/R, colorectal carcinoma DLD1-TxR, and glioma U87-TxR. In addition, we explored how these molecular and phenotypic alterations influence the anticancer effect of new drugs. Cytogenetic analysis showed polyploidy reduction after development of MDR in U87-TxR. Losses of 6q in all resistant cancer cell lines and inactivation of p53 in U87-TxR and PTEN in DLD1-TxR were also revealed. Overexpression of P-gp was observed in all MDR cancer cell lines. We evaluated the anticancer activities and MDR reversal potential of Akt inhibitor GSK690693, Ras inhibitor Tipifarnib, and two P-gp inhibitors (jatrophane diterpenoids). Their effects vary due to the cell-type differences, existence of MDR phenotype, presence of mdr1 SNP, and tumor suppressors' alterations. Tipifarnib and jatrophane diterpenoids significantly sensitized MDR cancer cells to paclitaxel. In conclusion, investigated MDR cancer cells obtained new molecular and cytogenetic characteristics that may serve as potential clinical prognostic markers. In addition, these MDR cancer cell lines present a valuable model for preclinical evaluation of new anticancer agents.",
publisher = "Springer, New York",
journal = "Cancer Chemotherapy and Pharmacology",
title = "Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing",
volume = "72",
number = "3",
pages = "683-697",
doi = "10.1007/s00280-013-2247-1"
}

Podolski-Renic, A., Jadranin, M., Stankovic, T., Bankovic, J., Stojkovic, S., Chiourea, M., Aljančić, I., Vajs, V., Tešević, V., Ruzdijic, S., Gagos, S., Tanic, N.,& Pešić, M.. (2013). Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing. in Cancer Chemotherapy and Pharmacology
Springer, New York., 72(3), 683-697.
https://doi.org/10.1007/s00280-013-2247-1

Podolski-Renic A, Jadranin M, Stankovic T, Bankovic J, Stojkovic S, Chiourea M, Aljančić I, Vajs V, Tešević V, Ruzdijic S, Gagos S, Tanic N, Pešić M. Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing. in Cancer Chemotherapy and Pharmacology. 2013;72(3):683-697.
doi:10.1007/s00280-013-2247-1 .

Podolski-Renic, Ana, Jadranin, Milka, Stankovic, Tijana, Bankovic, Jasna, Stojkovic, Sonja, Chiourea, Maria, Aljančić, Ivana, Vajs, Vlatka, Tešević, Vele, Ruzdijic, Sabera, Gagos, Sarantis, Tanic, Nikola, Pešić, Milica, "Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing" in Cancer Chemotherapy and Pharmacology, 72, no. 3 (2013):683-697,
https://doi.org/10.1007/s00280-013-2247-1 . .