Phenethyl isothiocyanate induced apoptosis via down regulation of Bcl-2/XIAP and triggering of the mitochondrial pathway in MCF-7 cells.

Abstract

Although isothiocyanates have been shown to inhibit carcinogen-induced tumorigenesis, no studies have been made to determine their therapeutic potential for the treatment of breast cancer. In the present study, we evaluated the apoptotic activities of phenethyl isothiocyanate (PEITC) in human breast cancer MCF-7 cells. Exposure to PEITC potently reduced cell viability. In addition, DNA fragments and TUNEL positive nuclei were detected in PEITC-treated cells. Furthermore, PEITC induced apoptosis via activation of caspases 7 and 9 and the cleavage of PARP, and these effects were reversed by treatment with the caspase inhibitor, Z-VAD-fmk. PEITC also caused a decrease in the levels of Bcl-2 with a concomitant increase in Bax levels, which resulted in the release of cytochrome c. XIAP suppression and Smac translocation also contributed to the PEITC-induced apoptosis. However, PEITC did not increase the expressions of p53 and p21. Taken together, the results of this study demonstrate that PEITC significantly induces apoptosis via a mitochondrial pathway. Specifically, PEITC induced a change in the Bax/Bcl-2 ratios, XIAP levels and Smac translocation that was conjunction with the release of cytochrome c and following caspase activation. Therefore, PEITC has the potential for use as a therapeutic agent for the treatment of breast cancer.

• Authors: Ji Won Lee, Min Kyung Cho
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 31 Issue 12 Pg. 1604-12 (Dec 2008) ISSN: 0253-6269 [Print] Korea (South)
• PMID: 19099231 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticarcinogenic Agents
• Isothiocyanates
• X-Linked Inhibitor of Apoptosis Protein
• phenethyl isothiocyanate
• Cytochromes c
• Poly(ADP-ribose) Polymerases
• Caspases

Topics

• Anticarcinogenic Agents (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Caspases (metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cytochromes c (metabolism)
• DNA Fragmentation
• Down-Regulation (drug effects)
• Enzyme Activation
• Gene Expression (drug effects)
• Genes, bcl-2 (drug effects)
• Genes, p53 (drug effects)
• Humans
• In Situ Nick-End Labeling
• Isothiocyanates (pharmacology)
• Mitochondria (drug effects)
• Poly(ADP-ribose) Polymerases (metabolism)
• Signal Transduction (drug effects)
• X-Linked Inhibitor of Apoptosis Protein (genetics)