Piperine promotes ultraviolet (UV)-B-induced cell death in B16F10 mouse melanoma cells through modulation of major regulators of cell survival

Abstract

An increase in the incidence of melanoma and its resistance to currently applied treatment regimes enhance the need for novel therapeutic agents and treatment modalities. In this study, we report that piperine, the most widely consumed dietary alkaloid, promotes cell death in ultraviolet (UV)-B-irradiated B16F10 mouse melanoma cells through the elevation of intracellular reactive oxygen species (ROS) formation, calcium homeostasis imbalance, and loss of mitochondrial membrane potential. Promotion of UVB-induced cell death by piperine was further revealed by caspase activations, poly(ADP) ribose polymerase cleavage, DNA fragmentation, and an increase in sub-G1 cells. Piperine promoted UVB-induced translocation of Bax from cytosol to mitochondria, accelerated an increase in the ratio of Bax to that of Bcl-2, and up-regulated the expression of apoptosis-inducing factor (AIF). These effects of piperine on UVB-irradiated cells were associated with apparent alterations in the expression of mitogen activated protein (MAP) kinase family proteins and PI3K–Akt survival signals. Piperine disrupted NF-κB signaling, inhibited UVB-induced nuclear translocation of NF-κB, and potentially reversed multi drug resistance (MDR) by reducing UVB-induced p-glycoprotein activity. Taken together, these results suggest the possibility of using piperine in combination with UVB as a possible therapeutic option for melanoma.