الفهرس 
Synthesis of Novel Hybrid Steroids with Possible Cytotoxicity and Pro-apoptotic Effects on Human Hepatocellular Carcinoma In vitro
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Abstract
A series of pregnenolone derivatives were synthesized and evaluated for anti-cancer activity against hepatocellular carcinoma cell line (HepG2). The synthesized steroidal derivatives 3, 4, 5, 6, 7, 8a and 8b were assessed for their cytotoxic activities using MTT (3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide) assay. Apoptotic activity was evaluated using dual acridine orange/ethidium bromide staining method and DNA fragmentation assay. The expression level of the pro-apoptotic genes Bak and Bax as well as anti-apoptotic genes Bcl-xL and Bcl-2 were analyzed using quantitative real time PCR. The results showed that compounds 4 and 6 exhibited cytotoxic activity (IC50s, 36.97 ± 2.18 and 18.46 ± 0.64 oM, respectively), whereas compounds 5 and 7 displayed weak cytotoxic activity (IC50s, 93.87 ± 8.30 oM and 93.48 ± 4.14 oM, respectively). All synthesized pregnenolone derivatives induced apoptosis through DNA fragmentation. Compounds 4 and 6 increased early and late apoptotic cell percentages while compounds 3, 5, 7 and 8b increased either early or late apoptotic cell percentage