title: Hinokitiol inhibits cell growth through induction of S-phase arrest and apoptosis in human colon cancer cells and suppresses tumor growth in a mouse xenograft experiment.
abstract: Hinokitiol (1), a tropolone-related natural compound, induces apoptosis and has anti-inflammatory, antioxidant, and antitumor activities. In this study, the inhibitory effects of 1 were investigated on human colon cancer cell growth and tumor formation of xenograft mice. HCT-116 and SW-620 cells derived from human colon cancers were found to be similarly susceptible to 1, with IC50 values of 4.5 and 4.4 μM, respectively. Compound 1 induced S-phase arrest in the cell cycle progression and decreased the expression levels of cyclin A, cyclin E, and Cdk2. Conversely, 1 increased the expression of p21, a Cdk inhibitor. Compound 1 decreased Bcl-2 expression and increased the expression of Bax, and cleaved caspase-9 and -3. The effect of 1 on tumor formation when administered orally was evaluated in male BALB/c-nude mice implanted intradermally separately with HCT-116 and SW-620 cells. Tumor volumes and tumor weights in the mice treated with 1 (100 mg/kg) were decreased in both cases. These results suggest that the suppression of tumor formation by compound 1 in human colon cancer may occur through cell cycle arrest and apoptosis.
authors.affiliation: Department of Biology Education, College of Education, Chungbuk National University , Cheongju 361-763, Korea.
authors.forename: Youn-Sun
authors.initials: YS
authors.lastname: Lee
authors.forename: Kyeong-Mi
authors.initials: KM
authors.lastname: Choi
authors.forename: Wonkyun
authors.initials: W
authors.lastname: Kim
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Jeon
authors.forename: Yong-Moon
authors.initials: YM
authors.lastname: Lee
authors.forename: Jin-Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Yeo-Pyo
authors.initials: YP
authors.lastname: Yun
authors.forename: Hwan-Soo
authors.initials: HS
authors.lastname: Yoo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019254:Genes, bcl-2 / Q000187:drug effects / Q000235:genetics; D045325:HCT116 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology*; D016196:S Phase / Q000187:drug effects*; D014334:Tropolone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays; D020741:rho GTP-Binding Proteins / Q000187:drug effects
chemical_list: D039821:Monoterpenes; D014334:Tropolone; D020741:rho GTP-Binding Proteins; C009479:beta-thujaplicin