CR229, a novel derivative of beta-carbolin-1-one, induces cell cycle arrest and apoptosis in HeLa cells via p53 activation.
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.
Kim
Min Kyoung
MK
Department of Medical Genetics, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, Korea.
Oh
Ha Lim
HL
Choi
Bu-Young
BY
Lim
Haeyoung
H
Cho
Youl-Hee
YH
Lee
Chul-Hoon
CH
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*
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