HY-2, a novel DNA topoisomerase II inhibitor, induces G2/M cell cycle arrest in HCT-116 cells

Abstract

4beta-(Benzoylthioureido)-4′-demethyl-4-desoxypodophyllotoxin (HY-2), a synthetic aroylthiourea analog of podophyllotoxin, was identified as a novel DNA topoisomerase II inhibitor. It exhibited significant antiproliferative effect on seven cancer cell lines and induced HCT-116 cells apoptosis. DNA flow cytometric analysis revealed that HY-2 induced cell cycle arrest at G2/M phase. Western blot analysis indicated that phosphorylation of cdc2 protein was decreased after HY-2 treatment, which might be the main cause for G2/M phase arrest.

Keywords:

• Podophyllotoxin
• G2/M arrest
• Cdc2
• Apoptosis

Acknowledgements

The studies in the laboratories were supported by the Natural Science Foundation of Jiangsu Province (BK2011390), Natural Science Foundation of Nantong City (K2010024), Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and National Natural Science Foundation of China (Grant No. 30971197 & 31171143), 973 Program (2011CB510004).