A novel small-molecule activator of procaspase-3 induces apoptosis in cancer cells and reduces tumor growth in human breast, liver and gallbladder cancer xenografts.

ABSTRACT:

Purpose

Procaspase-3, a proenzyme of apoptotic executioner caspase-3, is overexpressed in numerous tumors. We aimed to characterize a novel procaspase-3 activator, WF-210, which may have potential as an anticancer drug.

Experimental design

The procaspase-3 activating ability, antitumor efficacy, mechanisms of action, and toxicity profiles of WF-210 were investigated in vitro and in vivo, using normal cells, cancer cells, and mouse xenograft models. The role of procaspase-3 in WF-210-induced apoptosis was explored by manipulating procaspase-3 expression in cultured cells.

Results

WF-210 activated procaspase-3 with an EC50 of 0.95 μM, less than half that of its mother compound PAC-1 (2.08 μM). The mechanism involved the chelation of inhibitory zinc ions, subsequently re

SUBMITTER: Wang F 

PROVIDER: S-EPMC5528581 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature