title: Menthol induces cell-cycle arrest in PC-3 cells by down-regulating G2/M genes, including polo-like kinase 1.
abstract: Menthol, a naturally occurring monoterpene, is used in foods, cosmetic products, and topical therapeutic preparations. It also exerts cytotoxic activity against several cancer cell types, including prostate cancer cells. However, little is known about the mechanism of menthol action against prostate cancer cells. In this study, we investigated the effect of menthol on the gene expression profile of PC-3 prostate cancer cells using DNA microarray analyses. Gene set enrichment analysis revealed that menthol primarily affects the expression of cell cycle-related genes. Subsequent experimental analyses validated that menthol induces G2/M arrest. Particularly, menthol markedly down-regulated polo-like kinase 1 (PLK1), a key regulator of G2/M phase progression and inhibited its downstream signaling. Our computational analyses and experimental validation provide a basis for future investigations that are aimed at elucidating the action of menthol on cell cycle control in prostate cancer cells.
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Su-Hwa
authors.initials: SH
authors.lastname: Kim
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Lee
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Piccolo
authors.forename: Kristina
authors.initials: K
authors.lastname: Allen-Brady
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Jung Nyeo
authors.initials: JN
authors.lastname: Chun
authors.forename: Tae Woo
authors.initials: TW
authors.lastname: Kim
authors.forename: Nam-Hyuk
authors.initials: NH
authors.lastname: Cho
authors.forename: In-Gyu
authors.initials: IG
authors.lastname: Kim
authors.forename: Insuk
authors.initials: I
authors.lastname: So
authors.forename: Ju-Hong
authors.initials: JH
authors.lastname: Jeon
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D002455:Cell Division / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation; D016195:G2 Phase / Q000187:drug effects* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008610:Menthol / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D000097869:Polo-Like Kinase 1
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D008610:Menthol; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1