Open AccessCR229, a novel derivative of β‐carbolin‐1‐one, induces cell cycle arrest and apoptosis in HeLa cells via p53 activation
Author(s) -
Kim Min Kyoung,
Oh Ha Lim,
Choi BuYoung,
Lim Haeyoung,
Cho YoulHee,
Lee ChulHoon
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00552.x
Subject(s) - hela , apoptosis , cell cycle checkpoint , cell cycle , microbiology and biotechnology , flow cytometry , cyclin , cyclin b1 , chemistry , cyclin a , cell growth , cyclin dependent kinase 1 , cyclin d1 , programmed cell death , kinase , biology , cell , biochemistry
In the course of screening for novel anticancer compounds, CR229 (6‐Bromo‐2,3,4,9‐tetrahydro‐carbolin‐1‐one), a novel derivative of β‐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 µM 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. ( Cancer Sci 2007; 98: 1402–1407)