Biological investigation was conducted to study in vitro antiproliferative and pro-apoptotic potential of selected 17α-picolyl and 17(E)-picolinylidene
androstane derivatives. The antiproliferative impact was examined on six human tumor cell lines, including two types of breast (MCF-7 and MDA-MB-231), prostate (PC3), cervical (HeLa), colon (HT 29) and
lung cancer (A549), as well as one normal fetal lung fibroblasts cell line (MRC-5). All derivatives selectively decreased proliferation of
estrogen receptor negative MDA-MB-231
breast cancer cells after 48 h and 72 h treatment and compounds showed time-dependent activity. We used this cell line to investigate cell cycle modulation and apoptotic cell death induction by flow cytometry, expression of apoptotic
proteins by Western blot and apoptotic morphology by visual observation. Tested
androstane derivatives affected the cell cycle distribution and induced apoptosis and
necrosis. Compounds had different and specific mode of action, depending on derivative type and exposure time. Some compounds induced significant apoptosis measured by
Annexin V test compared to reference compound
formestane. Higher expression of pro-apoptotic BAX, downregulation of anti-apoptotic Bcl-2 and cleavage of PARP
protein were confirmed in almost all treated samples, but the lack of
caspase-3 activation suggested the induction of apoptosis in
caspase-independent manner. More cells with apoptotic morphology were observed in samples after prolonged treatment. Structure-activity relationship analysis was performed to find correlations between the structure variations of investigated derivatives and observed
biological effects. Results of this study showed that some of the investigated
androstane derivatives have good biomedical potential and could be candidates for anticancer
drug development.