In the present study, by employing in vitro cell culture and an in vivo melanoma xenograft model, we found that an alkaloid isolated from the roots of Cryptolepis sanguinolenta significantly inhibits mitochondrial biogenesis in melanoma cells by inducing mitochondrial fission, reducing enhancers of mitochondrial biogenesis and affecting mTOR signaling, as summarized in Fig. 8. This evidence concerns the gene MTOR and melanoma.