Effect of sulforaphane and 5-aza-2'-deoxycytidine on melanoma cell growth

Background: UV exposure-induced oxidative stress is implicated as the driving mechanism for melanoma. Increased oxidative stress results in DNA damage and epigenetic modifications. We wondered whether a low dose of antioxidant could attenuate the oxidative stress of and help cells respond to epigenetic modification treatment at a lower dose. Sulforaphane (SFN) is a natural bioactivated product of the cruciferous family and is known as an antioxidant. We investigated the combinational effect of SFN and epigenetic modification drug, 5-aza-2'-deoxycytidine (DAC), on metastatic melanoma growth. Methods: Cell growth characteristics, RNA-seq and histone post-translational modification markers (PTMs) were compared in single and combination treatments. Results: We found increased cell growth inhibition and changes in gene expression profiles which includes a key immuno-regulator cytokine, C-C motif ligand 5 (CCL-5) gene expression upon combinational treatments. There was no significant difference in detectable histone PTMs between treatments. Conclusions: These results indicate a potential combinational effect of a dietary antioxidant and an FDA-approved epigenetic drug in controlling melanoma growth. The long-term goal of the current study is to find the therapeutic role of the dietary antioxidant SFN as a supporting drug for targeted epigenetic treatment with DAC in controlling melanoma growth. mRNA profiles of mouse B16F10 melanoma cells treated with DMSO (control) , DAC, SFN, or combination treatment (DAC + SFN) were generated by deep sequencing using illumina's NextSeq 500 instrument (75bp SE reads). Three independent biological repeats were performed for all sample groups.