Indirubin 3'-Epoxide Induces Caspase-Independent Cell Death in Human Neuroblastoma.


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.

DOI: 10.1248/bpb.b15-00999

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@article{Kurita2016Indirubin3I, title={Indirubin 3'-Epoxide Induces Caspase-Independent Cell Death in Human Neuroblastoma.}, author={Masahiro Kurita and Satoshi Hanada and Yoshimi Ichimaru and Hiroaki Saito and Keiichi Tabata and Satoru Asami and Shinichi Miyairi and Takashi Suzuki}, journal={Biological & pharmaceutical bulletin}, year={2016}, volume={39 6}, pages={993-9} }