自噬
色胺
孕烯醇酮
细胞凋亡
类固醇
程序性细胞死亡
细胞内
化学
细胞生物学
生物
体外
生物化学
激素
作者
Jan Panada,Valeriya Klopava,Tatsiana Kulahava,Siarhei Koran,Yaroslav V. Faletrov,Н. С. Фролова,Elena Fomina,В. М. Шкуматов
出处
期刊:Steroids
[Elsevier]
日期:2023-12-01
卷期号:200: 109326-109326
标识
DOI:10.1016/j.steroids.2023.109326
摘要
In a previous work, we reported the synthesis of four novel indole steroids and their effect on rat C6 glioma proliferation in vitro. The steroid derived from dehydroepiandrosterone and tryptamine (IS-1) was the most active (52 % inhibition at 10 µM), followed by one of the epimers derived from pregnenolone and tryptamine (IS-3, 36 % inhibition at 10 µM). By contrast, the steroid derived from estrone and tryptamine (IS-2) showed negligible activity at 10 µM. No necrosis, increase in intracellular calcium or ROS levels was observed. In this work, the effect of compounds on C6 glioma apoptosis and autophagy is examined by fluorimetry and fluorescent microscopy. The IS-3 epimers disrupt the mitochondrial membrane potential and induce apoptosis in vitro moderately whereas IS-1 and IS-2 do not. However, IS-1 produces a large increase in monodansylcadaverine-positive autophagic vesicles over 24 h. The antiproliferative effect of indole steroids is ameliorated by autophagy inhibitor hydroxychloroquine, suggesting an autophagy-dependent mechanism of cell death.
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