Abstract LB-182: Combination of sulforaphane and 5-aza-2′-deoxycytidine slows the growth and upregulates the chemoattractant CCL5 in metastatic melanoma

Abstract

Abstract UV exposure-induced oxidative stress is implicated as a driving mechanism for melanoma. Increased oxidative stress results in DNA damage and epigenetic dysregulation. We previously found that a low dose of the antioxidant sulforaphane (SFN) in combination with the epigenetic drug 5 –aza –2 ′–deoxycytidine (DAC) slowed cell growth in melanoma at a greater rate than DAC alone. Here, we report a multi –omics analysis with combination and single drug treatment. We observed a significant increase in global protein abundance with an altered level of expression in the combination treatment as compared to individual treatment. Proteins associated with methylation patterns and with reactive oxidative species were found dysregulated in combination treatment. A comparison analysis of proteomic and transcriptomic data with Ingenuity Pathway Analysis showed common canonical pathways involved in phosphorylation (ERK/MAPK signaling) and immune response with combination treatment. The global DNA methylation pattern was analyzed to explore the impact of combination and single drug treatment on methylation status. Interestingly, we observed an increase in the levels of a critical immuno-regulator cytokine, C –C motif ligand 5 (CCL5), which functions as a chemoattractant for natural killer (NK) cells. Animal studies showed the level of CCL5in blood and tumor was increased with DAC and SFN combination treatment compared to that of control, which coincided with tumor reduction. Our data demonstrate the impact of SFN on the effectiveness of the FDA –approved drug DAC to reduce metastatic melanoma tumors. Citation Format: Tung-Chin Chiang, Brian Koss, Aaron J. Storey, Jovanny Zabaleta, Samrat Roy Choudhury, Bradley D. Shields, Elizabeth C. Draper, L Joseph Su, Alan J. Tackett. Combination of sulforaphane and 5-aza-2′-deoxycytidine slows the growth and upregulates the chemoattractant CCL5 in metastatic melanoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-182.