Steroid dimers-In vitro cytotoxic and antimicrobial activities
Abstract
The in vitro cytotoxic activity of previously synthesized steroid dimers with different spacer group (sulfide, trithiolane ring or phosphorotrithioate) and the substituent at C-17 position was tested for their possible effects against following human tumor cell lines: cervical adenocarcinoma (HeLa), chronic myelogenous leukemia (K562) and two human breast cancer cell lines (MDA-MB-361 and MDA-MB-453). These compounds, applied at micromolar concentrations, exhibited cytotoxic activity of different intensity (compared with cisplatin as a control), modality and selectivity in these malignant cell lines. The best activity against all four cell cancer lines was exhibited by dimer-sulfides. All screened compounds exerted concentration-dependent cytotoxic activity against leukemia K562 cells. The compounds which exerted the most pronounced cytotoxic action exhibited notably higher cytotoxic activities against K562, HeLa and MDA-MB-453 cells in comparison to resting and PHA-stimulated PBMC, po...inting to a significant selectivity in their antitumor actions. Examination of the mechanisms of cytotoxicity on leukemia K562 cells revealed pro-apoptotic action of each of the investigated compounds applied at concentrations 2IC(50). The most prominent pro-apoptotic action was exhibited by dimer-sulfide of cholest-4-en-3-one. Furthermore, almost all of the tested compounds at IC50 concentrations induced G1 phase cell cycle arrest in K562 cells. Antimicrobial activity against Gram-positive, Gram-negative bacteria and fungal cells, and toxicity to brine shrimp Artemia sauna, were evaluated. There was no antibacterial activity. The best antifungal activity was exhibited against Saccharomyces cerevisiae by dimers linked with trithiolane ring, indicating a selective activity of investigated compounds.
Keywords:
Steroid dimers / cytotoxic activity / Cell death / Cell cycle analysis / Caspase / Antimicrobial activitySource:
Journal of Steroid Biochemistry and Molecular Biology, 2014, 143, 365-375Publisher:
- Oxford : Pergamon-Elsevier Science Ltd
Funding / projects:
- Interactions of natural products, their derivatives and coordination compounds with proteins and nucleic acids (RS-MESTD-Basic Research (BR or ON)-172055)
- Biological response modifiers in physiological and pathological conditions (RS-MESTD-Basic Research (BR or ON)-175011)
DOI: 10.1016/j.jsbmb.2014.06.005
ISSN: 0960-0760
PubMed: 24923733
WoS: 000341465500040
Scopus: 2-s2.0-84902667382
Collections
Institution/Community
IHTMTY - JOUR AU - Krstić, Natalija AU - Matić, Ivana Z. AU - Juranić, Zorica AU - Novaković, Irena AU - Sladić, Dušan PY - 2014 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/1409 AB - The in vitro cytotoxic activity of previously synthesized steroid dimers with different spacer group (sulfide, trithiolane ring or phosphorotrithioate) and the substituent at C-17 position was tested for their possible effects against following human tumor cell lines: cervical adenocarcinoma (HeLa), chronic myelogenous leukemia (K562) and two human breast cancer cell lines (MDA-MB-361 and MDA-MB-453). These compounds, applied at micromolar concentrations, exhibited cytotoxic activity of different intensity (compared with cisplatin as a control), modality and selectivity in these malignant cell lines. The best activity against all four cell cancer lines was exhibited by dimer-sulfides. All screened compounds exerted concentration-dependent cytotoxic activity against leukemia K562 cells. The compounds which exerted the most pronounced cytotoxic action exhibited notably higher cytotoxic activities against K562, HeLa and MDA-MB-453 cells in comparison to resting and PHA-stimulated PBMC, pointing to a significant selectivity in their antitumor actions. Examination of the mechanisms of cytotoxicity on leukemia K562 cells revealed pro-apoptotic action of each of the investigated compounds applied at concentrations 2IC(50). The most prominent pro-apoptotic action was exhibited by dimer-sulfide of cholest-4-en-3-one. Furthermore, almost all of the tested compounds at IC50 concentrations induced G1 phase cell cycle arrest in K562 cells. Antimicrobial activity against Gram-positive, Gram-negative bacteria and fungal cells, and toxicity to brine shrimp Artemia sauna, were evaluated. There was no antibacterial activity. The best antifungal activity was exhibited against Saccharomyces cerevisiae by dimers linked with trithiolane ring, indicating a selective activity of investigated compounds. PB - Oxford : Pergamon-Elsevier Science Ltd T2 - Journal of Steroid Biochemistry and Molecular Biology T1 - Steroid dimers-In vitro cytotoxic and antimicrobial activities VL - 143 SP - 365 EP - 375 DO - 10.1016/j.jsbmb.2014.06.005 ER -
@article{ author = "Krstić, Natalija and Matić, Ivana Z. and Juranić, Zorica and Novaković, Irena and Sladić, Dušan", year = "2014", abstract = "The in vitro cytotoxic activity of previously synthesized steroid dimers with different spacer group (sulfide, trithiolane ring or phosphorotrithioate) and the substituent at C-17 position was tested for their possible effects against following human tumor cell lines: cervical adenocarcinoma (HeLa), chronic myelogenous leukemia (K562) and two human breast cancer cell lines (MDA-MB-361 and MDA-MB-453). These compounds, applied at micromolar concentrations, exhibited cytotoxic activity of different intensity (compared with cisplatin as a control), modality and selectivity in these malignant cell lines. The best activity against all four cell cancer lines was exhibited by dimer-sulfides. All screened compounds exerted concentration-dependent cytotoxic activity against leukemia K562 cells. The compounds which exerted the most pronounced cytotoxic action exhibited notably higher cytotoxic activities against K562, HeLa and MDA-MB-453 cells in comparison to resting and PHA-stimulated PBMC, pointing to a significant selectivity in their antitumor actions. Examination of the mechanisms of cytotoxicity on leukemia K562 cells revealed pro-apoptotic action of each of the investigated compounds applied at concentrations 2IC(50). The most prominent pro-apoptotic action was exhibited by dimer-sulfide of cholest-4-en-3-one. Furthermore, almost all of the tested compounds at IC50 concentrations induced G1 phase cell cycle arrest in K562 cells. Antimicrobial activity against Gram-positive, Gram-negative bacteria and fungal cells, and toxicity to brine shrimp Artemia sauna, were evaluated. There was no antibacterial activity. The best antifungal activity was exhibited against Saccharomyces cerevisiae by dimers linked with trithiolane ring, indicating a selective activity of investigated compounds.", publisher = "Oxford : Pergamon-Elsevier Science Ltd", journal = "Journal of Steroid Biochemistry and Molecular Biology", title = "Steroid dimers-In vitro cytotoxic and antimicrobial activities", volume = "143", pages = "365-375", doi = "10.1016/j.jsbmb.2014.06.005" }
Krstić, N., Matić, I. Z., Juranić, Z., Novaković, I.,& Sladić, D.. (2014). Steroid dimers-In vitro cytotoxic and antimicrobial activities. in Journal of Steroid Biochemistry and Molecular Biology Oxford : Pergamon-Elsevier Science Ltd., 143, 365-375. https://doi.org/10.1016/j.jsbmb.2014.06.005
Krstić N, Matić IZ, Juranić Z, Novaković I, Sladić D. Steroid dimers-In vitro cytotoxic and antimicrobial activities. in Journal of Steroid Biochemistry and Molecular Biology. 2014;143:365-375. doi:10.1016/j.jsbmb.2014.06.005 .
Krstić, Natalija, Matić, Ivana Z., Juranić, Zorica, Novaković, Irena, Sladić, Dušan, "Steroid dimers-In vitro cytotoxic and antimicrobial activities" in Journal of Steroid Biochemistry and Molecular Biology, 143 (2014):365-375, https://doi.org/10.1016/j.jsbmb.2014.06.005 . .