Apoptosis Induced by a New Member of Saponin Family Is Mediated through Caspase-8-Dependent Cleavage of Bcl-2

Authors:
Zhu J, Xiong L, Yu B and Wu J
In:
Source: Mol Pharmacol
Publication Date: (2005)
Issue: 68(6): 1831-1838
Research Area:
Cancer Research/Cell Biology
Platform:
Nucleofectorâ„¢ I/II/2b
Abstract
OSW-1 is a new member of cholestane saponin family, which is cytotoxic against many types of malignant cells. The present works showed that OSW-1 induced apoptosis of mammalian cells in a concentration- and time- dependent manner. The drug-induced apoptosis was mediated through mitochondrial pathway, in which significant Bcl-2 cleavage was induced. This drug-induced Bcl-2 cleavage in CHO cells could be suppressed either by introducing dominant negative caspase-8 or by caspase-8 inhibitor, suggesting that the Bcl-2 cleavage is caspase-8 dependent, whereas this cleavage was independent of caspase-3 activity. The inhibition of caspase-8 activity also resulted in the reduction of apoptotic cells, indicating that Bcl-2 cleavage induced by caspase-8 promotes the progression of apoptosis. Furthermore, Yeast two-hybrid and co-immunoprecipitation assays showed that the small subunit of caspase-8 interacted directly with Bcl-2. The overexpression of caspase-8 small subunit reduced the cleavage of Bcl-2 and inhibited the apoptosis induced by OSW-1. Taken together, OSW-1 can induce apoptosis of mammalian cells, in which the caspase-8 dependent cleavage of Bcl-2 plays an important role.