We aimed to explore the effects of low concentration of 1,3,7-trimethylxanthine(caffeine)on melanoma cells,as well as the underlying mechanism.In this work,B16F10 murine melanoma cells were pre-treated with different concentrations(0,50,100,200,400 or 600 μM)of caffeine for 24 h,48 h,or 72 h.The cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.The migration and invasion assay were assessed by Transwell system.The cell apoptosis were analyzed by Annexin V-Cy5 and propidium iodide(PI)staining.The protein levels of bone morphogenetic protein(BMP)2,BMP4,BMP7,B-cell lymphoma(Bcl-2),and Bax were measured by Western blot.The results showed that caffeine(400 or 600 μM)pretreatment significantly reduced the cell viability at 48 h and 72 h(P < 0.05 or P < 0.01)but not at 24 h.The number of migrated and invaded cells was significantly decreased by caffeine(200,400 or 600 μM)(P < 0.05 or P < 0.01).Moreover,the percentages of apoptotic cells were statistically increased by 200,400 or 600 μM of caffeine(P < 0.05 or P < 0.01).We also observed caffeine(200,400 or 600 μM)significantly down-regulated the levels of BMP2 and BMP4 but not BMP7,and statistically down-regulated the ratio of Bcl-2 to Bax(P < 0.05 or P < 0.01).To conclude,low concentration of caffeine inhibits cell viability,migration and invasion,and induces cell apoptosis of B16F10 melanoma cells.