Endostar induces apoptotic effects in HUVECs through activation of caspase-3 and decrease of Bcl-2.
BACKGROUND
Endostar is a novel recombinant human endostatin expressed and purified in Escherichia coli with the N-terminal modified. It has been shown that endostar inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) through the membrane surface receptor KDR/flt-1(VEGFR-2, vascular endothelial growth factor receptor-2) by exerting anti-angiogenesis effects. But the molecular mechanism remained unclear.


METHODS
The apoptotic effects induced by endostar in the serum-deprived situation were investigated by 4'-6-diaminidino-2-phenylindole (DAPI) staining and the Annexin V-fluorescein isothiocyanate (FITC) binding assay. The mechanism of action was explored by Western blotting assay.


RESULTS
Endostar induced remarkable apoptosis in HUVECs. The expressions of apoptosis-related proteins showed that caspase-3 was activated, but caspase-8, a marker of the non-mitochondria-mediated apoptosis signal pathway, was not. Further investigation revealed that cellular Bcl-2 decreased in the endostar-treated groups, while the level of Bax was almost unchanged.


CONCLUSIONS
Endostar induces apoptotic effects in HUVECs through the activation of caspase-3 and a decrease of the Bcl-2 to Bax ratio.
Ling
Yun
Y
Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009 People's Republic of China.
Lu
Na
N
Gao
Ying
Y
Chen
Yan
Y
Wang
Sen
S
Yang
Yong
Y
Guo
Qinglong
Q