Sulforaphane induces cytotoxicity and lysosome- and mitochondria-dependent cell death in colon cancer cells with deleted p53
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
21557998
DOI
10.1016/j.tiv.2011.04.019
PII: S0887-2333(11)00115-9
Knihovny.cz E-resources
- MeSH
- Anticarcinogenic Agents toxicity MeSH
- Time Factors MeSH
- Gene Deletion MeSH
- Stress, Physiological drug effects MeSH
- HCT116 Cells MeSH
- Isothiocyanates MeSH
- Humans MeSH
- Lysosomes drug effects metabolism MeSH
- MAP Kinase Kinase 4 genetics metabolism MeSH
- Mitochondria drug effects metabolism MeSH
- Tumor Suppressor Protein p53 genetics metabolism MeSH
- Colonic Neoplasms genetics metabolism prevention & control MeSH
- DNA Damage drug effects MeSH
- Cell Proliferation drug effects MeSH
- bcl-2-Associated X Protein genetics metabolism MeSH
- Heat-Shock Proteins genetics metabolism MeSH
- Gene Expression Regulation, Neoplastic drug effects MeSH
- Sulfoxides MeSH
- Thiocyanates toxicity MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Anticarcinogenic Agents MeSH
- BAX protein, human MeSH Browser
- Isothiocyanates MeSH
- MAP Kinase Kinase 4 MeSH
- Tumor Suppressor Protein p53 MeSH
- bcl-2-Associated X Protein MeSH
- Heat-Shock Proteins MeSH
- sulforaphane MeSH Browser
- Sulfoxides MeSH
- Thiocyanates MeSH
Mechanisms and pathways responsible for cytotoxicity of sulforaphane (SF) in colon cancer cells with deleted p53 were investigated during 48 h 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.
References provided by Crossref.org
