Abstract 703: Caffeine modulates the cell cycle in cancer cells to enhance cisplatin efficacy.

Abstract

Abstract Caffeine has been shown to enhance the efficacy of chemotherapy, but the mechanism is not well understood. In this study, we investigated cell-cycle modulation induced by caffeine in combination with cisplatinum treatment of human cancer cells. Proliferation inhibition was determined with a clonogenic assay. Mitotic and apoptotic changes were observed by imaging of 143B dual-color cells, in which GFP is expressed in the nucleus and RFP in the cytoplasm. Modulation of the cell-cycle in combination with cisplatinum was observed using time-lapse imaging analyses of HeLa cells expressing a fluorescent cell-cycle indicator, FUCCI (Fluorescent Ubiquitination-based Cell Cycle Indicator). The clonogenic assay showed that caffeine increased the efficacy of cisplatin on inhibition of cell proliferation. Dual-color imaging demonstrated that cisplatin decreased mitosis and induced apoptosis in 143B cells. The combination of cisplatin and caffeine reduced the decrease of mitosis and increased apoptosis. Time-lapse FUCCI imaging showed that cisplatin strongly induced cell-cycle arrest at the S/G2/M phases in HeLa cells. Caffeine released the cell-cycle arrest induced by cisplatin, resulting in increased cell-killing efficacy. These data indicates that caffeine can effectively modulates the cell-cycle in cancer cells treated with cisplatin and possibly other drugs. Citation Format: Shinji Miwa, Shuya Yano, Yukihiko Hiroshima, Yasunori Tome, Fuminori Uehara, Sumiyuki Mii, Hiroaki Kimura, Katsuro Hayashi, Hiroyuki Tsuchiya, Michelle Digman, Enrico Gratton, Robert M. Hoffman. Caffeine modulates the cell cycle in cancer cells to enhance cisplatin efficacy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 703. doi:10.1158/1538-7445.AM2013-703