The therapeutic potential of resveratrol in a mouse model of melanoma lung metastasis.

• Melanoma tends to aggressively invade adjoining tissue and spread to distant organs e.g. liver lung, bone and brain. • Resveratrol significantly decreased angiogenesis and frequency of regulatory T cells in the lungs. • Resveratrol significantly increased tumor cell apoptosis and trafficking of activated T cells to lungs. Resveratrol is an anticancer phytochemical polyphenol isolated from a natural origin, without any significant side effects. Resveratrol was investigated in immunocompetent mice with regards to its possible effect on lung cancer metastasis. Cytotoxicity was assessed in three melanoma cell lines (B16F10, B6, and A375) by administration of 20 and 40 μM resveratrol. B16F10 cells were transfected with pT-tdTomato vector to express red fluorescent protein (RFP). RFP-B16F10 cells were injected IV into 3 groups of 20 C57BL/6 mice (ten for tests and others for survival). The three groups include PBS, no treatment, and resveratrol 40 mg/kg IP (4X/week for 3 weeks). Lung tissues were analyzed by TUNEL assay, Western blot, and immunohistochemistry. The in vitro growth of all melanoma cell lines was significantly suppressed by 40 μM resveratrol for 3 days. The mean survival rate of mice was enhanced and the lung tumor growth was inhibited by in vivo IP injection of 40 mg/kg resveratrol. Increased CXCL10 and IFN-γ levels and decreased angiogenesis and less tumor infiltration by Tregs were found in the lung tumors. In conclusion, lung metastasis of melanoma was effectively inhibited by resveratrol treatment. [ABSTRACT FROM AUTHOR]