title: CR229, a novel derivative of beta-carbolin-1-one, induces cell cycle arrest and apoptosis in HeLa cells via p53 activation.
abstract: In the course of screening for novel anticancer compounds, CR229 (6-Bromo-2,3,4,9-tetrahydro-carbolin-1-one), a novel derivative of beta-carbolin-1-one, was generated as a new scaffold candidate. For the first time, the authors demonstrate that CR229 inhibited the growth of HeLa cells by the induction of cell cycle arrest and apoptosis. Analysis of flow cytometry and western blots of HeLa cells treated with 2.5 microM CR229 revealed an appreciable cell cycle arrest in the G1, G2/M phase and apoptotic induction via the p53-dependent pathway. Furthermore, the release of cytochrome c from mitochondria was detected using confocal microscopy in HeLa cells treated with CR229. Accordingly, these data demonstrate that the anticancer activity of CR229 is associated with: (i) the down-regulation of cyclins and cyclin-dependent kinase; (ii) the induction of p53, p21, and p16; and (iii) the activation of caspase-3.
authors.affiliation: Department of Medical Genetics, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, Korea.
authors.forename: Min Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Ha Lim
authors.initials: HL
authors.lastname: Oh
authors.forename: Bu-Young
authors.initials: BY
authors.lastname: Choi
authors.forename: Haeyoung
authors.initials: H
authors.lastname: Lim
authors.forename: Youl-Hee
authors.initials: YH
authors.lastname: Cho
authors.forename: Chul-Hoon
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D006131:Growth Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: C523550:6-bromo-2,3,4,9-tetrahydrocarbolin-1-one; D000970:Antineoplastic Agents; D002243:Carbolines; D006131:Growth Inhibitors; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D053148:Caspase 3