Introduction: Malignant melanoma is a type of skin cancer which is caused by occurrence of mutations in DNA of the epidermis’ basal layers. According to Warburg theory, the growth of cancer cells is dependent on the aerobic glycolysis. Glycolysis pathway has been reported to increase in cancerous cells significantly. Vitamin C, a water-soluble vitamin, acts as a potent glycolysis inhibitor by targeting glyceraldehyde-3-phosphate dehydrogenase and depleting the NAD pool. Recent studies showed that a high dose of vitamin C can be prescribed as a supplementary medicine in order to increase the cytotoxicity of the chemotherapeutic drugs against some types of cancers. METHODS: In this study, human melanoma A375 cells were treated with ciprofloxacin -CIP- at a concentration of 5 μg mL-1 for two weeks. Exponentially grown cells in medium containing 5 μg mL-1 of CIP were designated as ciprofloxacin-resistant A375 cells and named A375-CIP5. MTT assay was used to investigate the cytotoxicity of vitamin C on A375-CIP5 and parental A375 cells. The potential of colony formation and migration of A375-CIP5 and A375 cells were also evaluated at serum concentration of vitamin C -0.05 mM- by colony formation and wound healing assays, respectively. RESULTS: The IC50 values of vitamin C on A375 and A375-CIP5 cells at 48 h were 0.53 and 0.16 mM, respectively. The migration ability of A375-CIP5 cells was significantly lower than that of A375 cells. At serum concentration, vitamin C could markedly decrease the mobility of A375 cells while no changed in the potential of A375-CIP5 cells to close the scratch wound was observed at 72 h after wound incision. Moreover, A375-CIP5 exhibited higher colony formation potential as compared to that of parental cells. The plating efficiency of A375-CIP5 and A375 cells were decreased at serum concentration of vitamin C. CONCLUSION: Taken together, for the first time, we report that vitamin C at a concentration present in serum seems to have anti-proliferative and anti-migration activity against melanoma A375 cells. The short-term anti-proliferation potential of vitamin C on CIP-resistant A375 cells was higher than that of parental cells while the influence of vitamin C on colony formation capacity of CIP-resistant A375 cells was the same as that of A375.

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