Sulforaphane induces cell death in colon cancer cells. - GreenMedInfo Summary
Sulforaphane induces cytotoxicity and lysosome- and mitochondria-dependent cell death in colon cancer cells with deleted p53.
Toxicol In Vitro. 2011 Oct ;25(7):1302-9. Epub 2011 May 1. PMID: 21557998
Department of Medical Biology and Genetics, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Simkova 870, 500 38 Hradec Kralove, Czech Republic.
Mechanisms and pathways responsible for cytotoxicity of sulforaphane (SF) in colon cancer cells with deleted p53 were investigated during 48h of exposure. SF showed dose-dependent cytotoxicity and proapoptotic activity in the present model. In addition, in HCT-116 p53KO cells SF induced DNA damage with the subsequent cellular response and signaling not including p53 and caspase-2 pathways. Conversely, in SF-treated cells JNK was activated which led to an early lysosomal membrane permeabilization, release of cathepsin B and D and activation of Bid by specific cleavage. Concomitantly, the expression of Bax increased in the presence of JNK-mediated Bcl-2 inhibition which was followed by mitochondrial release of cytochrome c and activation of apoptosis. These results suggest that SF may be useful as a chemopreventive agent in colon cancer with inactivated or lost p53.