CR229, a novel derivative of β‐carbolin‐1‐one, induces cell cycle arrest and apoptosis in HeLa cells via p53 activation

• Published in: Cancer science 2007-09, Vol.98 (9), p.1402-1407
• Main Authors: Kim, Min Kyoung, Oh, Ha Lim, Choi, Bu‐Young, Lim, Haeyoung, Cho, Youl‐Hee, Lee, Chul‐Hoon
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Apoptosis - genetics; Biological and medical sciences; Carbolines - chemistry; Carbolines - pharmacology; Caspase 3 - metabolism; Cell Cycle - drug effects; Cell Cycle - genetics; Cell Line; Cell Line, Tumor; Cell Proliferation - drug effects; Down-Regulation - drug effects; Down-Regulation - genetics; General aspects; Growth Inhibitors - chemistry; Growth Inhibitors - pharmacology; HeLa Cells; Humans; Medical sciences; Original; Pharmacology. Drug treatments; RNA, Small Interfering - genetics; Tumor Suppressor Protein p53 - antagonists & inhibitors; Tumor Suppressor Protein p53 - biosynthesis; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumors
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/j.1349-7006.2007.00552.x

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)