Shinji Miwa and Shuya Yano contributed equally to this work.
Dynamic color-coded fluorescence imaging of the cell-cycle phase, mitosis, and apoptosis demonstrates how caffeine modulates cisplatinum efficacy
Article first published online: 12 SEP 2013
© 2013 Wiley Periodicals, Inc.
Journal of Cellular Biochemistry
Volume 114, Issue 11, pages 2454–2460, November 2013
How to Cite
Miwa, S., Yano, S., Tome, Y., Sugimoto, N., Hiroshima, Y., Uehara, F., Mii, S., Kimura, H., Hayashi, K., Efimova, E. V., Fujiwara, T., Tsuchiya, H. and Hoffman, R. M. (2013), Dynamic color-coded fluorescence imaging of the cell-cycle phase, mitosis, and apoptosis demonstrates how caffeine modulates cisplatinum efficacy. J. Cell. Biochem., 114: 2454–2460. doi: 10.1002/jcb.24593
None of the authors have a conflict of interest regarding this study.
- Issue published online: 12 SEP 2013
- Article first published online: 12 SEP 2013
- Accepted manuscript online: 20 MAY 2013 09:53AM EST
- Manuscript Accepted: 1 MAY 2013
- Manuscript Received: 21 MAR 2013
- NCI. Grant Numbers: CA126023, CA164492
- CELL CYCLE;
- FLUORESCENCE IMAGING;
Caffeine enhances the effect of certain anticancer drugs, but the mechanism of modulation is poorly understood. In this study, modulation of cisplatinum efficacy induced by caffeine was visualized at the subcellular level by real-time fluorescent-protein imaging. Mitotic and apoptotic changes were observed by imaging 143B human osteosarcoma dual-color cells, in which GFP is expressed in the nucleus and RFP is expressed in the cytoplasm. Modulation of the cell cycle was imaged using time-lapse imaging of HeLa cells expressing a fluorescent ubiquitination-based cell cycle indicator (FUCCI) in the nucleus. Clonogenic assays showed that caffeine increased the inhibition by cisplatinum on cell proliferation. Subcellular imaging demonstrated that cisplatinum decreased mitosis and induced apoptosis in 143B cells. The combination of cisplatinum and caffeine enhanced mitosis and subsequently increased apoptosis. Time-lapse imaging showed that cisplatinum strongly induced cell-cycle arrest in the S/G2 phase in HeLa-FUCCI cells. Caffeine overcame the cell-cycle arrest induced by cisplatinum, thereby increasing its efficacy, since cisplatinum is ineffective against quiescent cells. The data in this report indicate that caffeine modulates the cell cycle in cancer cells, thereby enhancing efficacy of cell-cycle-dependent anticancer drugs such as cisplatinum. J. Cell. Biochem. 114: 2454–2460, 2013. © 2013 Wiley Periodicals, Inc.