title: Capsaicin-mediated tNOX (ENOX2) up-regulation enhances cell proliferation and migration in vitro and in vivo.
abstract: Cancer chemoprevention is employed to block or reverse the progression of malignancies. To date, several thousands of agents have been found to possess chemopreventative activity, one of which is capsaicin, a component of chili peppers that exhibits antigrowth activity against various cancer cell lines. However, the role of capsaicin in tumorigenesis remains controversial because both cancer prevention and promotion have been proposed. Here, we made the unexpected discovery that treatment with low concentrations of capsaicin up-regulates tNOX (tumor-associated NADH oxidase) expression in HCT116 human colon carcinoma cells in association with enhanced cell proliferation and migration, as evidenced by down-regulation of epithelial markers and up-regulation of mesenchymal markers. Importantly, tNOX-knockdown in HCT116 cells by RNA interference reversed capsaicin-induced cell proliferation and migration in vitro and decreased tumor growth in vivo. Collectively, these findings provide a basis for explaining the tumor-promoting effect of capsaicin and might imply that caution should be taken when using capsaicin as a chemopreventive agent.
authors.affiliation: Graduate Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan, Republic of China.
authors.forename: Nei-Chi
authors.initials: NC
authors.lastname: Liu
authors.forename: Pei-Fang
authors.initials: PF
authors.lastname: Hsieh
authors.forename: Ming-Kun
authors.initials: MK
authors.lastname: Hsieh
authors.forename: Zih-Ming
authors.initials: ZM
authors.lastname: Zeng
authors.forename: Hsiao-Ling
authors.initials: HL
authors.lastname: Cheng
authors.forename: Jiunn-Wang
authors.initials: JW
authors.lastname: Liao
authors.forename: Pin Ju
authors.initials: PJ
authors.lastname: Chueh
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology*; D002212:Capsicum / Q000737:chemistry*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D009247:NADH, NADPH Oxidoreductases; C431909:tumor-associated NADH oxidase; D002211:Capsaicin