Mechanism of colon cancer cell apoptosis induced by telocinobufagin: role of oxidative stress and apoptosis pathway.
- Author:
Shun-Tian LIANG
1
;
Yuan LI
;
Xiao-Wu LI
;
Jun-Jiang WANG
;
Fu-Xian TAN
;
Qin-Rui HAN
;
Lu LI
;
Xue-Qing YAO
;
Xue-Gang SUN
Author Information
- Publication Type:Journal Article
- MeSH: Apoptosis; Bufanolides; pharmacology; Caspase 9; metabolism; Cell Survival; Colorectal Neoplasms; pathology; Humans; MAP Kinase Kinase Kinases; metabolism; NF-KappaB Inhibitor alpha; metabolism; Oxidative Stress; Poly (ADP-Ribose) Polymerase-1; metabolism; Tumor Cells, Cultured; Tumor Suppressor Protein p53; metabolism; bcl-2-Associated X Protein; metabolism; bcl-Associated Death Protein; metabolism
- From: Journal of Southern Medical University 2016;36(7):921-926
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effects of telocinobufagin on viability and apoptosis of colorectal cancer (CRC) cells and explore the mechanism of telocinobufagin-induced apoptosis.
METHODSMTT assay was performed to detect the viability of CRC cells exposed to telocinobufagin. Nuclear staining with Hoechst 33342 and flow cytometry were used to analyze the cell death of CRC cells. Expressions of proteins related with cell apoptosis and oxidative stress were determined with Western blotting.
RESULTSTelocinobufagin decreased the viability of CRC cells in a time- and dose-dependent manner. The presence of karyopycnosis and apoptotic bodies together with the results of flow cytometry suggested that telocinobufagin induced cell apoptosis to cause cell death. Western blotting showed that telocinobufagin exposure of the cells resulted in upregulated p53 and Bax protein expressions and promoted cleavage of caspase 9 and PARP. Telocinobufagin induced phosphorylation of Bad and PARP cleavage, and suppressed phosphorylation of IKBα and TAK1 and expression of survivin in the cells.
CONCLUSIONTelocinobufagin can decrease the viability of CRC cells by inducing cell apoptosis, which involves p53-mediated Bax activation and inhibition of the IAP pathway.
