RRC ID |
51755
|
著者 |
Kurita M, Hanada S, Ichimaru Y, Saito H, Tabata K, Asami S, Miyairi S, Suzuki T.
|
タイトル |
Indirubin 3'-Epoxide Induces Caspase-Independent Cell Death in Human Neuroblastoma.
|
ジャーナル |
Biol Pharm Bull
|
Abstract |
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.
|
巻・号 |
39(6)
|
ページ |
993-9
|
公開日 |
2016-1-1
|
DOI |
10.1248/bpb.b15-00999
|
PMID |
27251501
|
MeSH |
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Apoptosis Regulatory Proteins / metabolism
Caspases / metabolism
Cell Cycle / drug effects
Cell Line, Tumor
DNA Fragmentation
Humans
Indoles / pharmacology*
Neuroblastoma / pathology
|
IF |
1.863
|
引用数 |
7
|
リソース情報 |
ヒト・動物細胞 |
SK-N-SH(RCB0426) |