Abstract LB-168: Genistein sensitizes radio-resistant cancer cells through regulation of NF-kappaB

Abstract

Abstract Background: NF-kappaB is a key transcription factor involved in the control of normal cellular and organismal processes, such as immune and inflammatory responses, developmental processes, cellular growth, and apoptosis. However, NF-kappaB is persistently active in a number of disease states, including cancer. It has been reported that chemo- or radio- resistant cancer cells had elevated NF-kappaB activity. Recent studies including ours have showed that genistein, a soy-derived isoflavonoid, has antitumor activity in various cancer cells. Objective: In this study, we evaluated whether genistein could sensitize ionizing radiation resistance of cervical cancer cells through regulation of NF-kappaB. Methods: Six cervical cancer cell lines (HeLa, CaSki, C33A, ME180, SiHa, HeLa229) were treated by 20 Gy radiation with 50 M genistein or not. Cell growth rate was measured by MTT assay and protein expression level was analyzed by western blotting. Protein localization was observed by confocal microscopic analysis. NF-kappaB transcriptional activity was measured by luciferase reporter gene assay. NF-kappaB DNA binding activity was evaluated by electophoretic mobility shift assay. Results: Among six cervical cancer cells, HeLa and HeLa229 cells showed radio-resistance accompanied by elevated NF-kappaB activity. Ionizing radiation induced NF-kappaB nuclear transclocation and stimulated NF-kappaB DNA binding and transcriptional activities. However, pretreatment with genistein inhibited radiation induced transcriptional activity coincident to decreased radio-resistancy. Genistein also inhibited radiation-induced NF-kappaB regulated anti-apoptotic gene expression including c-myc, Survivin, XIAP, Bcl-2, IAP-1, TRAF, A1/Bfl-1 and FLIP. Conclusion: Taken together, genistein can sensitize radio-resistant cancer cells through regulation of NF-kappaB and could be used as a radio-sensitizer for the treatment of cervical cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-168.