Indole-3-carbinol and ultraviolet B induce apoptosis of human melanoma cells via down-regulation of MITF

Abstract

We investigated the mechanism of indole-3-carbinol (I3C)/ultraviolet B (UVB)-induced apoptosis using SK-MEL-2 and SK-MEL-5 human melanoma cells. I3C/UVB significantly reduced the viability of SK-MEL-2 cells, whereas it had little influence on SK-MEL-5 cells. Correspondingly, cell cycle analysis showed that I3C/UVB induced a clear increase in the sub-G(0)/a(1) phase in SK-MEL-2 cells. Furthermore, I3C/UVB activated caspase-9, caspase-8, caspase-3, and Bid and caused the cleavage of poly(ADP-ribose) polymerase (PARP) in SK-MEL-2 cells. In contrast, I3C/UVB showed no effects on the apoptotic signaling pathways in SK-MEL-5 cells. Moreover, we found that I3C down-regulated the microphthalmia-associated transcription factor (MITF) in SK-MEL-2 cells, but not in SK-MEL-5 cells. Next, to investigate the involvement of MITF in I3C/UVB-induced apoptosis, MITF silencing was conducted using small interfering RNA (siRNA) for MITF in SK-MEL-5 cells. Interestingly, I3C/UVB dramatically decreased the viability of MITF-down-regulated SK-MEL-5 cells. These results indicate that MITF plays a critical role in melanoma cell survival.