Because melanogenesis is inherently toxic and uniquely expressed in the melanin-containing cells, therapy focusing on melanogenesis can become a specific molecular target to melanoma cells without significant systemic side effects. N-propionyl-4-S-cysteaminylphenol (NPr-4-S-CAP) is selectively incorporated into melanoma cells for the substrate of tyrosinase and causes cytotoxicity against them. We have previously demonstrated that NPr-4-S-CAP selectively induces apoptosis to pigmented melanomas accompayed by caspase 3 activation and DNA fragmentation and how reactive oxygen species (ROS) were generated in this’s process (Ishii-Osai Y et al: J Dermatol Sci, 2012). It has been reported that ROS mediates inductions of p53, the redox sensor Trx-ASK1 and the Fas/Fas ligand that may result in the apoptotic cell death.
In this study, we aimed to elucidate the detection of the molecules and the analysis of molecular mechanisms related to apoptosis by NPr-4-S-CAP. Western blot analysis and real-time RT-PCR did not detect increased Nuclear factor E2-relted factor 2 (Nrf2) or Heme Oxygenase-1 (HO-1) in two human melanoma cell lines cultured in the presence of NPr-4-S-CAP. We, then, analyzed cDNA species induces in the NPr-4-S-CAP treated 70W melanoma cells by using cDNA microarray. Results indicated that expressions of thirteen candidate genes includinding TNF receptor- and p53-associated proteins were increased in association with NPr-4-S-CAP-mediated apoptosis. This suggests that in the process of NPr-4-S-CAP-mediated apoptosis, several cellular genes related to apoptosis induced but protective Nrf2/HO-1 genes were not induced in human melanoma cells.