Cytotoxic Effect of Spondias cytherea Fruit Extract in Murine Melanoma Model In Vivo and In Vitro.

Cancer is a disease resulting from the deregulation of cell growth control, caused by an interaction between dietary, genetic, and environmental risk factors. Melanoma accounts for about 4% of cancers diagnosed; however they represent 75% of skin cancer-related deaths, with the incidence and death rates having increased globally over the past few decades. Spondias cytherea is a plant from the family Anacardiaceae. Its usage in the treatment of wounds, sores, and burns is reported from several countries, but the anticancer effects of the fruit have not yet been studied. We thus set out to evaluate the effects of S. cytherea fruit extract (SpE) on the epithelial to mesenchymal transition in the mouse melanoma model. B16-F10 cells cultured in varying concentrations of SpE showed a dose-dependent reduction in the ability to form colonies, which then migrate to fill up the wounded area. SpE downregulated the expression of AKT/nuclear factor kappa B/cyclooxygenase-2 (Akt/NF-κB/COX-2) responsible for cell proliferation, and reduced CD133 expression. This led to in vivo tumor shrinkage at the dose of 450 mg/kg body weight (bw). Low-level expression of vimentin on mesenchymal cells and increased E-cadherin expression on epithelial cells were observed in treated cells. The number of vasculogenic mimicry tubes that formed also decreased significantly at 450 mg/kg bw. These results suggest that S. cytherea fruit can become a useful source for chemotherapeutic drugs in the future.