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  - 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 . .