Abstract
Piper capense belongs to Piperaceae family and has long been used as a traditional medicine to treat various diseases in several parts of Africa. The present study aims to investigate the effect of Piper capense fruit extract (PCFE) alone and in combination with dacarbazine on metastatic melanoma cell line B16-F10 and in vivo in C57BL/6J mice. Cytotoxic effects of PCFE alone and in association with dacarbazine on B16-F10 cells were studied by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and colony formation assay. Wound healing assay, immunofluorescence staining, and western blot analysis were performed to evaluate the individual and combined effect of PCFE and dacarbazine on epithelial-mesenchymal transition (EMT). For in vivo studies, C57BL/6J mice were subcutaneously injected with B16-F10 cells (5 × 105 cells/mL), and the effect of PCFE and dacarbazine was studied on tumor development. The alteration of EMT was evaluated by targeting E-cadherin, vimentin, and CD133 in PCFE alone and in combination with dacarbazine-treated tumor tissues by western blot analysis. Phytochemical screening of PCFE reveals the presence of certain secondary metabolites. Our results showed that PCFE alone and in association with dacarbazine has a good activity in preventing B16-F10 melanoma cell progression and clonogenicity. This extract also regulated EMT. In vivo results showed that PCFE (100 mg/kg body weight) reduced tumor size in C57BL/6J mice along with the decrease in the expression of vasculogenic mimicry (VM) tubes as well as an improvement in the qualitative and quantitative expression of markers involved in EMT. Our study suggests that PCFE may be useful for managing the growth and metastasis of melanoma.