Histone Deacetylase Inhibitor RG2833 Reduces the Viability of Human Malignant Melanoma Cell Lines SK-MEL-5 and SK-MEL-28 \u3cem\u3eIn Vitro\u3c/em\u3e

Histone deacetylases (HDACs) play an important role in the epigenetic control of gene expression in both normal and cancer cells. Previous studies have demonstrated that pharmaceutical inhibition of HDACs can kill and/or suppress the growth of cancer cells. RG2833 is a HDAC inhibitor that targets specific HDACs known to be active in cancer cells. Melanoma cells have previously been shown to respond to HDAC inhibitors that are structurally similar to RG2833. We hypothesized that the inhibition of HDAC activity by RG2833 would result in the reduced growth and/or death of cells from the malignant melanoma cell lines SK-MEL-5 and SK-MEL-28. To test our hypothesis, we exposed SK-MEL-5 and SK-MEL-28 cells to increasing concentrations of RG2833. We found that concentrations of RG2833 that effectively inhibited HDAC activity in melanoma cells also resulted in altered gene expression profiles and reduced cell proliferation and viability. In our studies, we employed three different and commonly used assays to measure cell viability: 1) SRB, which measures total cellular protein, 2) AlamarBlue®, which is reduced to a fluorescent product in live cells, and 3) CellTiter-GloTM, which generates a luminescent signal proportional to the amount of cellular ATP present. Interestingly, the choice of assay used to measure cell viability had a significant impact on the results with the more sensitive assays yielding results that indicate a greater sensitivity of the melanoma cells to RG2833. Together, these results demonstrate the effectiveness of RG2833 in altering gene expression and reducing the growth and viability of malignant melanoma cells in vitro and warrant further investigation of the potential therapeutic use of RG2833 and related compounds in the battle against cancer