文章基本信息

标题：Indirubin 3′-Epoxide Induces Caspase-Independent Cell Death in Human Neuroblastoma
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作者：Masahiro Kurita ; Satoshi Hanada ; Yoshimi Ichimaru 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2016
卷号：39
期号：6
页码：993-999
DOI：10.1248/bpb.b15-00999
出版社：The Pharmaceutical Society of Japan
摘要：Indirubin inhibits cyclin-dependent kinases by binding to their ATP-binding site, thereby exerting potent cytotoxicity on some tumor cells. We examined the anti-tumor effect of indirubin 3′-epoxide on human neuroblastoma cell lines (IMR-32, SK-N-SH, and NB-39). The results revealed potent cytotoxicity of indirubin 3′-epoxide against the IMR-32 (IC₅₀: 0.16 µM) and SK-N-SH (IC₅₀: 0.07 µM) cells. Furthermore, it also induced an increase of the sub-G₁ population in the IMR-32 cells. Examination by Hoechst 33342 staining revealed apoptosis characterized by cell shrinkage, nuclear condensation and nuclear fragmentation in a concentration-dependent manner. Furthermore, annexin V–propidium iodide (PI) double-staining revealed an increase in the percentage of early apoptotic cells following treatment of the cells with indirubin 3′-epoxide without activation of caspases. In addition, significant decreases in the protein level of survivin and poly(ADP-ribose)polymerase (PARP), and increase in that of apoptosis-inducing factor (AIF) were found in the nuclei of the cells. These results suggest that indirubin 3′-epoxide induced caspase-independent apoptosis through mechanisms involving DNA fragmentation and inhibition of DNA repair.