AS, YZ, XDZ, MAS: Performed the immunohistochemical studies on human skin and derived cancers. AS, SHG, SS: Performed the studies on MT-3 expression in NHEK, HaCaT, and Human Melanocytes. DAS: Designed the study, organized group meetings, provided core facility support, and wrote BGB324 the manuscript with assistance (SHG) and graduate student (AS). The authors declare that there are no conflicts of interest. The research described

was supported by funds provided by the Department of Pathology and the School of Medicine and Health Sciences, University of North Dakota. Undergraduate research, student mentoring, core facilities for bioinformatics and statistics, and gene expression were supported by the ND INBRE program project, P20 RR016471 from the National Center for Research Resources and P20 GM103442 from the National Institute of General Medical Sciences, NIH. “
“The tumor suppressor p53 is generally PLX3397 nmr viewed as the most direct and promising anti-cancer target. Although p53 as a transcriptional

factor is best known for controlling the cell cycle and apoptosis, increasing evidence suggests that p53 is also involved in induction of autophagy (Guo et al., 2013). The pharmacological rescue of inactive p53 may therefore represent an attractive therapeutic approach. Pifithrin-alpha (PFT) is an inhibitor of p53 and is considered to be useful for therapeutic suppression in order to reduce cancer treatment side effects (Komarova and Gudkov, 1998) and to protect against various genotoxic agents (Komarova et al., 2003). Several reports have shown that PFT blocks the p53-mediated selleckchem activation of autophagy caused by chemical agents (Dong et al., 2012 and Zhu et al., 2011). PFT has been validated as a useful p53 inhibitor for the elucidation of p53 functions in experimental studies. It has been observed that docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, causes cancer cell death via apoptosis (Gleissman et al., 2010, Lim et al., 2009 and Wendel

and Heller, 2009). Along with apoptosis, autophagy has been indicated to play a role in the cytotoxic mechanisms of DHA in recent reports (Jing et al., 2011, Rovito et al., 2013 and Yao et al., 2014). Autophagy and apoptosis are self-destructive processes that share many key regulators, such as reactive oxygen species (ROS). Physiological levels of ROS lead to growth adaption and survival; however, excess ROS cause irreversible cellular damage, thus provoking autophagy and/or apoptosis (Droge, 2002 and Rubio et al., 2012). It has been shown that production of ROS is a key mediator of DHA-induced cytotoxicity (Arita et al., 2001 and Maziere et al., 1999). A previous report has also shown that DHA-induced cytotoxicity is mediated by oxidative stress, and the cytotoxic effects are abrogated by typical antioxidants (Kanno et al., 2011).