Abstract B26: Combinational effect of sulforaphane (SFN) and epigenetic demethylation agent 5-aza-2’-deoxycytidine (DAC) on metastatic melanoma

Abstract

Abstract UV exposure-induced oxidative stress is implicated as the driving mechanism of melanoma development. Increased oxidative stress results in imbalanced reactive oxygen species (ROS) that damage DNA and dysregulated epigenetic modifications and leads to melanoma progression. Sulforaphane (SFN) is the natural bioactivated product of the cruciferous vegetable family (e.g., broccoli and Brussels sprouts) and is known to play a dual role in cytoprotection and to induce apoptosis in the tumor via antioxidant regulation and histone modification of epigenetic enzymes. We investigated the combinational effect of 5-aza-2’-deoxycytidine (DAC), an FDA-approved DNA-modification epigenetic drug and SFN in melanoma cells. We found further cell growth inhibition and an increased number of altered gene expression profiles, increased survival-related cytokine expression, as well as unique histones post-translational modifications (PTMs) upon combinational treatments compared to single treatment in vitro. These results set the stage for animal studies. The long-term goal of the current study is to find an optimal dietary dose of antioxidants from SFN to reduce the burden of oxidative stress, which may contribute to melanoma recurrence, a constant problem with current treatments. In addition to recurrence, a reduced dose of epigenetic drugs applied may minimize the side effects of single-high-dose treatment. Citation Format: Tung-chin Chiang, L. Joseph Su, Brian S. Koss, Charity Washam, Stephanie Byrum, Aaron Storey, Alan J. Koss. Combinational effect of sulforaphane (SFN) and epigenetic demethylation agent 5-aza-2’-deoxycytidine (DAC) on metastatic melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr B26.