Growth Inhibition and Differentiation of Murine Melanoma B16‐BL6 Cells Caused by the Combination of Cisplatin and Caffeine

We preliminarily investigated the combined effects of cisplatin and caffeine on murine melanoma B16‐BL6 cells in vitro. When caffeine was added before or simultaneously with cisplatin, there was little growth inhibition. The addition of 2.0 mM caffeine after 1 h of exposure to cisplatin inhibited growth and induced cell differentiation. This treatment resulted in fewer cells, and the numbers of melanosomes and mitochondria and the amount of Golgi's complex and endoplasmic reticulum were increased. DNA histograms obtained by flow cytometry showed that cells treated with cisplatin alone accumulated in the G(2)/M phase, with a partial G(2) block. The addition of 2.0 mM caffeine after 1 h of treatment with cisplatin reduced this block. Caffeine caused murine melanoma B16‐BL6 cells treated with cisplatin to differentiate, and this inhibited growth.