Inhibition of proliferation and induction of G1-phase cell-cycle arrest by dFMGEN, a novel genistein derivative, in lung carcinoma A549 cells. (April 2013)

• Record Type: Journal Article
• Authors: Peng, Bo; Cao, Jianguo; Yi, Sisi; Wang, Chengkun; Zheng, Guopei; He, Zhimin
• Is Part Of: Drug and chemical toxicology. Volume 36:Number 2(2013:Apr.)
• Page Start: 196
• Page End: 204
• Publication Date: 2013-04
• Subjects: Toxicology -- Periodicals; Drugs -- Toxicology -- Periodicals; Toxicology, Experimental -- Periodicals; 615.9005
• DOI: 10.3109/01480545.2012.710620
• Languages: English
• ISSNs: 0148-0545

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>Genistein (GEN) is a molecule of great interest as a potent chemopreventive agent against atherosclerosis and cancer. However, the bioavailability of GEN is very low <italic>in vivo</italic>. Our previous study showed that a GEN derivative, 7-difluoromethyl-5, 4′-dimethoxygenistein (dFMGEN) has a better bioavailability than GEN <italic>in vivo</italic>. In this study, we further evaluated the efficacy of dFMGEN as a candidate for cancer therapy. We demonstrated that dFMGEN treatment decreased the viability of A549 cells in a concentration- and time-dependent manner and induced cell-cycle arrest at the G₁ phase. G₁ phase arrest was correlated with a significant reduction of Cdk4 and cyclin D1 protein level. Further studies showed that cyclin-dependent kinase (Cdk)4 and cyclin D1 protein-level decrease was caused by Cdk inhibitors p15, p21, and p27 level increase, and decreased protein level directly suppressed Rb protein phosphorylation and E2F-1 expression, then cell-cycle progression was arrested. Finally, we also found that dFMGEN has a dosage effect in suppressing tumor growth <italic>in vivo</italic>, and that dFMGEN was well tolerated by animals. In summary, our results suggest that dFMGEN has therapeutic potential for the treatment of human lung cancer.</p> </abstract>