title: The novel carboxamide analog ITR-284 induces caspase-dependent apoptotic cell death in human hepatocellular and colorectal cancer cells.
abstract: We have previously reported that ITR-284, a potent carboxamide-derived anticancer agent, induced apoptosis in leukemia cells. However, there are no reports showing that ITR-284 inhibits human hepatocellular and colorectal cancer cells. In this study, we investigated the antiproliferative effects and apoptotic induction of ITR-284 on various types of human hepatocellular and colorectal cancer cells in vitro. The growth inhibition effect of ITR-284 on cancer cells was evaluated by thiazolyl blue tetrazolium bromide (MTT) assay. Cell morphology was examined under a phase-contrast microscope. The activities of caspase-3, -8 and -9 were determined by caspase colorimetric assay. ITR-284 reduced the cell viability in human hepatocellular cancer cells (Hep G2, Hep 3B, SK-HEP-1 and J5) and colorectal cancer cells (HT 29, COLO 205, HCT 116 and SW 620). ITR-284 had highly selective effects on Hep 3B and COLO 205 cells. ITR-284 stimulated morphological changes of Hep 3B and COLO 205 cells. The activation of caspase-3, -8 and -9 contributed to ITR-284-induced apoptosis. ITR-284-triggered growth inhibition was significantly attenuated by the inhibitors of caspase-3, -8 and -9 in Hep 3B and COLO 205 cells. ITR-284 induced apoptosis in Hep 3B and COLO 205 cells through the caspase cascade-dependent signaling pathway.
authors.affiliation: Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan, ROC.
authors.forename: Yu-Ren
authors.initials: YR
authors.lastname: Liao
authors.forename: Chi-Cheng
authors.initials: CC
authors.lastname: Lu
authors.forename: Kuang-Chi
authors.initials: KC
authors.lastname: Lai
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.forename: Sheng-Chu
authors.initials: SC
authors.lastname: Kuo
authors.forename: Yen-Fang
authors.initials: YF
authors.lastname: Wen
authors.forename: Shinji
authors.initials: S
authors.lastname: Fushiya
authors.forename: Tian-Shung
authors.initials: TS
authors.lastname: Wu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology*; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000473:pathology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology*; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D061945:Caspase Inhibitors; C545715:N-(2-dimethylaminoethyl)-4,8-dihydrobenzo(1,2-b,4,5-b')dithiophene-2-carboxamide; D013876:Thiophenes; D020169:Caspases