We show that an enriched extract of H. vansoesti induced cell death in human melanoma cells with an IC50 value of 36.36 μg mL−1, by (i) triggering a pro-inflammatory response, (ii) activating extrinsic apoptosis mediated by tumor necrosis factor receptors triggering the mitochondrial apoptosis via the involvement of Bcl-2 proteins and caspase 9, and (iii) inducing a significant reduction in several proteins promoting human angiogenesis. Here, CASP9 is linked to melanoma.