Identification of a novel function of Id-1 in mediating the anticancer responses of SAMC, a water-soluble garlic derivative, in human bladder cancer cells.

Abstract

Studies have shown that the expression of inhibitor of differentiation (Id-1) is increased in bladder cancer and is associated with drug resistance. S-allylmercaptocysteine (SAMC), a water-soluble component of garlic, is known to have a potent therapeutic effect on human cancer. The aim of this study was to investigate whether Id-1 expression mediates SAMC-induced cell death in bladder cancer cells. After generating stable Id-1-expressing and si-Id-1 transfectants in various bladder cancer cell lines, cell sensitivity to SAMC was compared by colony formation and MTT assays. The results indicated that Id-1 overexpression reduced the positive effect of SAMC on cell survival, while the inactivation of Id-1 increased cellular susceptibility to SAMC. Using DAPI staining, the apoptosis of bladder cancer cells induced by SAMC was shown to be negatively regulated by Id-1 expression. The expression of apoptosis-related proteins analyzed by Western blotting further supported the negative role of Id-1 in SAMC-induced apoptosis. Furthermore, by wound closure and type I collagen invasion assays, the inhibitory effect of SAMC on the invasion and migration of bladder cancer cells was found to be associated with the down-regulation of Id-1. Our results demonstrated that SAMC-induced apoptosis is associated with the Id-1 pathway, and that the inactivation of Id-1 enhances the ability of SAMC to inhibit the survival, invasion and migration of bladder cancer cells. These findings may lead to the development of novel therapeutic strategies for the treatment of bladder cancer.

• Authors: Hao Hu, Xiao Peng Zhang, Yu Liang Wang, Chee Wai Chua, Sze Ue Luk, Yong Chuan Wong, Ming Tat Ling, Xiao Feng Wang, Ke Xin Xu
• Journal: Molecular medicine reports (Mol Med Rep) 2011 Jan-Feb Vol. 4 Issue 1 Pg. 9-16 ISSN: 1791-3004 [Electronic] Greece
• PMID: 21461556 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Inhibitor of Differentiation Protein 1
• S-allylmercaptocysteine
• Cysteine

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Cell Death (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cysteine (analogs & derivatives, pharmacology)
• Garlic (chemistry)
• Gene Expression Regulation, Neoplastic
• Humans
• Inhibitor of Differentiation Protein 1 (genetics, metabolism)
• Urinary Bladder Neoplasms (drug therapy, genetics)