Jan Panada , Valeriya Klopava , Tatsiana Kulahava , Siarhei Koran , Yaroslav Faletrov , Nina Frolova , Elena Fomina , Vladimir Shkumatov
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引用次数: 0
Abstract
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.
期刊介绍:
STEROIDS is an international research journal devoted to studies on all chemical and biological aspects of steroidal moieties. The journal focuses on both experimental and theoretical studies on the biology, chemistry, biosynthesis, metabolism, molecular biology, physiology and pharmacology of steroids and other molecules that target or regulate steroid receptors. Manuscripts presenting clinical research related to steroids, steroid drug development, comparative endocrinology of steroid hormones, investigations on the mechanism of steroid action and steroid chemistry are all appropriate for submission for peer review. STEROIDS publishes both original research and timely reviews. For details concerning the preparation of manuscripts see Instructions to Authors, which is published in each issue of the journal.