Phenethyl isothiocyanate (PEITC) promotes G2/M phase arrest via p53 expression and induces apoptosis through caspase- and mitochondria-dependent signaling pathways in human prostate cancer DU 145 cells.

Abstract

Phenethyl isothiocyanate (PEITC), one of many compounds found in cruciferous vegetables, has been reported as a potential anticancer agent. In earlier studies, PEITC was shown to inhibit cell growth and induction of apoptosis in many cancer cell lines. However, no report has shown whether PEITC can induce apoptosis in human prostate cancer cells. Herein, we aimed to determine whether PEITC has anticancer activity in DU 145 human prostate cancer cells. As a result, we found that PEITC induced a dose-dependent decrease in cell viability through induction of cell apoptosis and cell cycle arrest in the G(2)/M phase of DU 145 cells. PEITC induced morphological changes and DNA damage in DU 145 cells. The induction of G(2)/M phase arrest was mediated by the increase of p53 and WEE1 and it reduced the level of CDC25C protein. The induction of apoptosis was mediated by the activation of caspase-8-, caspase-9- and caspase-3-depedent pathways. Results also showed that PEITC caused mitochondrial dysfunction, increasing the release of cytochrome c and Endo G from mitochondria, and led cell apoptosis through a mitochondria-dependent signaling pathway. This study showed that PEITC might exhibit anticancer activity and become a potent agent for human prostate cancer cells in the future.

• Authors: Nou-Ying Tang, Ya-Ting Huang, Chun-Shu Yu, Yang-Ching Ko, Shin-Hwar Wu, Bin-Chuan Ji, Jai-Sing Yang, Jiun-Long Yang, Te-Chun Hsia, Ya-Yin Chen, Jing-Gung Chung
• Journal: Anticancer research (Anticancer Res) Vol. 31 Issue 5 Pg. 1691-702 (May 2011) ISSN: 1791-7530 [Electronic] Greece
• PMID: 21617228 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticarcinogenic Agents
• Isothiocyanates
• Reactive Oxygen Species
• phenethyl isothiocyanate
• Cytochromes c
• Caspases

Topics

• Anticarcinogenic Agents (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Caspases (metabolism)
• Cell Division (drug effects)
• Cell Proliferation (drug effects)
• Comet Assay
• Cytochromes c (metabolism)
• DNA Damage (drug effects)
• Flow Cytometry
• Fluorescent Antibody Technique
• G2 Phase (drug effects)
• Humans
• Isothiocyanates (pharmacology)
• Male
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, metabolism)
• Prostatic Neoplasms (drug therapy, pathology)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Tumor Cells, Cultured