Abstract
Background: UV exposure-induced oxidative stress is implicated as a driving mechanism for melanoma. Increased oxidative stress results in DNA damage and epigenetic dysregulation. Accordingly, we explored whether a low dose of the antioxidant sulforaphane (SFN) in combination with the epigenetic drug 5-aza-2’-deoxycytidine (DAC) could slow melanoma cell growth. SFN is a natural bioactivated product of the cruciferous family, while DAC is a DNA methyltransferase inhibitor. Methods: Melanoma cell growth characteristics, gene transcription profiles, and histone epigenetic modifications were measured after single and combination treatments with SFN and DAC. Results: We detected melanoma cell growth inhibition and specific changes in gene expression profiles upon combinational treatments with SFN and DAC, while no significant alterations in histone epigenetic modifications were observed. Dysregulated gene transcription of a key immunoregulator cytokine—C-C motif ligand 5 (CCL-5)—was validated. Conclusions: These results indicate a potential combinatorial effect of a dietary antioxidant and an FDA-approved epigenetic drug in controlling melanoma cell growth.
Highlights
While the incidence of certain cancer types has declined, the number of diagnosed melanoma cases has increased sharply over the past three decades [1,2]
A dose of 5 μM of SFN and 25 nM of DAC were chosen based on cell viability assays with more than 50% cells surviving from a single treatment of SFN and DAC
The combination treatment induced significant growth inhibition compared to any single treatment ( p < 0.03, Student’s t-test)
Summary
While the incidence of certain cancer types has declined, the number of diagnosed melanoma cases has increased sharply over the past three decades [1,2]. Synthesis of eumelanin leads to scavenges of reactive oxygen species (ROS) while the synthesis of pheomelanin leads to depletion of antioxidants and results in ROS accumulation [10,11,12]. This is in concert with the determination that people with pale skin. Methods: Melanoma cell growth characteristics, gene transcription profiles, and histone epigenetic modifications were measured after single and combination treatments with SFN and DAC. Results: We detected melanoma cell growth inhibition and specific changes in gene expression profiles upon combinational treatments with SFN and DAC, while no significant alterations in histone epigenetic modifications were observed. Conclusions: These results indicate a potential combinatorial effect of a dietary antioxidant and an FDA-approved epigenetic drug in controlling melanoma cell growth
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