title: Anticancer effects of KI-10F: a novel compound affecting apoptosis, angiogenesis and cell growth in colon cancer.
abstract: The anticancer effect of a new pyrazole derivative, KI-10F (2-(4-(2-(4-(dimethylamino)             phenyl)pyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol‑1-yl) acetonitrile)•3.5HCl)             was evaluated in human colon cancer cells. KI-10F strongly suppressed the growth             of human colon cancer cells and induced apoptosis by increasing the proportion             of sub-G1 presenting apoptotic cells as well as causing cell cycle arrest at the             G2/M phase. Apoptosis by KI-10F was confirmed by observation of an increase in             the expression of cleaved caspase-3, caspase-8, caspase-9 and Bax, and the decrease             of Bcl-2. Decreased expression of HIF-1α and VEGF, and the inhibition of HUVEC             tube formation and migration showed that KI-10F effectively inhibited the angiogenesis             process. Furthermore, in vivo study in a mouse xenograft model showed that KI-10F             produced a stronger antitumor activity than 5-FU, a conventional anticancer drug             prescribed for the treatment of colon cancer. The effects of KI-10F on tumor proliferation             (PCNA), angiogenesis (CD34) and apoptosis (cleaved caspase-3) were evaluated by             immunohistochemistry using isolated tumor tissue samples. Taken together, our             results demonstrated that KI-10F induces apoptosis and inhibits cell growth and             angiogenesis both in vitro and in vivo. We suggest that KI-10F is an effective             chemotherapeutic candidate for use against colon cancer.
authors.affiliation: NCEED and Department of Biomedical Sciences, College of Medicine, Inha University, Incheon 400-712, Republic of Korea. hongs@inha.ac.kr
authors.forename: Sang-Won
authors.initials: SW
authors.lastname: Hong
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Jung
authors.forename: Myung-Joo
authors.initials: MJ
authors.lastname: Choi
authors.forename: Da Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Hee-Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Zheng
authors.forename: Guang Yong
authors.initials: GY
authors.lastname: Li
authors.forename: Ibrahim M
authors.initials: IM
authors.lastname: El-Deeb
authors.forename: Byung Sun
authors.initials: BS
authors.lastname: Park
authors.forename: So Ha
authors.initials: SH
authors.lastname: Lee
authors.forename: Soon-Sun
authors.initials: SS
authors.lastname: Hong
mesh_terms: D000097:Acetonitriles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011720:Pyrazoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: C579033:2-(4-(2-(4-(dimethylamino)phenyl)pyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl)acetonitrile; D000097:Acetonitriles; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D011720:Pyrazoles