Effect of Sulforaphane and 5-Aza-2’-Deoxycytidine on Melanoma Cell Growth

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.

Natural Compounds as New Cancer Treatments

“…In this special issue original research manuscripts including both pure compounds and whole natural extracts have been included. Chiang et al [3] have used sulforaphane, natural molecules previously characterized as promising for fighting cancer [4], to challenge melanoma in combination with the epigenetic drug 5-aza-2′-deoxycytidine (DAC). In this manuscript, the authors have observed that the combination between DAC and sulforaphane reduces melanoma cell growth by changing gene expression profiles but without altering epigenetics.…”

Supplementary Materials from Epigenetic Control of <i>Cdkn2a.Arf</i> Protects Tumor-Infiltrating Lymphocytes from Metabolic Exhaustion

“…RNA sequencing RNA sequencing was carried out as before 4 . For total RNA-seq, the Sequence library was prepared from 500 ng of total RNA using Illumina's (San Diego, CA) TruSeq RNA Sample Preparation Kit v2 following the manufacturer's protocol.…”

Epigenetic Control of Cdkn2a.Arf Protects Tumor-Infiltrating Lymphocytes from Metabolic Exhaustion

“…RNA sequencing (RNA-seq) was carried out as before (27). For total RNA-seq, the Sequence library was prepared from 500 ng of total RNA using Illumina's TruSeq RNA Sample Preparation Kit v2 following the manufacturer's protocol.…”