title: Menthol inhibits the proliferation and motility of prostate cancer DU145 cells.
abstract: In recent years, the transient receptor potential melastatin member 8 (TRPM8) channel has emerged as a promising prognostic marker and putative therapeutic target in prostate cancer. We have found that forced overexpression of TRPM8 in PC-3 cells can inhibit the cell proliferation and motility probably through the TRPM8 activation. In this study, we aimed to investigate whether activating the TRPM8 channel by its selective agonist menthol can inhibit the proliferation and motility of androgen-independent prostate cancer (AIPC) with remarkable expression of TRPM8. Menthol is a naturally occurring compound, which has been widely used in cosmetics and pharmaceutical products, and also as flavoring in food. DU145 cells are androgen-independent but have a remarkable expression of TRPM8. The demonstration of the existence of TRPM8 and the absence of TRPA1 in DU145 cells provided the foundation for the following experiments, because both TRPM8 and TRPA1 are molecular targets of menthol. The outcome of MTT assay indicated that menthol inhibited the cell growth (p < 0.01). Cell cycle distribution and scratch assay analysis revealed that menthol induced cell cycle arrest at the G(0)/G(1) phase (p < 0.01). Furthermore, menthol inhibited the migration of DU145 cells by downregulating the focal-adhesion kinase. So it suggests that the activation of the existing TRPM8 channels may serve as a potential and pragmatic treatment for those AIPC with remarkable expression of TRPM8, and menthol is a useful compound for future development as an anticancer agent.
authors.affiliation: Department of Urology, Zhongnan Hospital, Wuhan University, Number 169, Donghu Road, Wuhan, Hubei, People's Republic of China.
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Wang
authors.forename: Xinghuan
authors.initials: X
authors.lastname: Wang
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Yang
authors.forename: Guangbin
authors.initials: G
authors.lastname: Zhu
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.forename: Zhe
authors.initials: Z
authors.lastname: Meng
mesh_terms: D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008610:Menthol / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D000074025:TRPA1 Cation Channel; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human; D050051:Transient Receptor Potential Channels; D008610:Menthol; D018844:Cyclin-Dependent Kinases