Effects of curcumin derivatives C085 on K562 cells and its mechanism
10.3969/j.issn.1001-1978.2015.06.026
- VernacularTitle:姜黄素衍生物C085对K562细胞的作用及机制研究
- Author:
Ying WU
;
Ruijia CHEN
;
Lixian WU
;
Jianhua XU
- Publication Type:Journal Article
- Keywords:
C085;
curcumin derivative;
IM;
BCR-ABL;
proliferation;
apoptosis;
mechanism
- From:
Chinese Pharmacological Bulletin
2015;(6):870-875
- CountryChina
- Language:Chinese
-
Abstract:
Aim To explore the anti-proliferation and apoptotic effects of C085, a curcumin derivative, on K562 cells and its mechanism. Methods MTT assay and flow cytometry were used to examine cell prolifera-tion and apoptosis, respectively. The phosphorylation levels of Bcr-Abl initiated signaling proteins were ana-lyzed using Western blot. Results The results showed that C085 suppressed the growth of K562 cells and the IC50 value was about 5-fold lower than that of Cur. C085 also induced significant apoptosis on K562 cells in 24 hours when compared with imatinib. Western blot results demonstrated that C085 down-regulated the phosphorylation of Bcr-Abl in K562 cells in a dose-de-pendent manner. The phosphorylation of Stat 5 and
Crkl, which were downstream signaling proteins of Bcr-Abl kinase, was also inhibited by C085. C085 caused the opening of mitochondrial PT holes as detected by JC-1 fluorescent, which inhibited Bcl-2 and enhanced Bax , then induced apoptosis. Conclusion C085 in-hibited BCR-ABL+ K562 cells through inhibiting BCR-ABL kinase activity and down-regulating its down-stream signal proteins. Directly acting on mitochondrial PT hole and then activating apoptosis- associated pro-teins are also involved in the pro-apoptotic effect of C085 .
