Effect of Sulforaphane and 5-Aza-2'-Deoxycytidine on Melanoma Cell Growth.
Effect of Sulforaphane and 5-Aza-2'-Deoxycytidine on Melanoma Cell Growth.
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DOI：
10.3390/medicines6030071
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发表时间：
2019-06-27
期刊：
影响因子：
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通讯作者：
Tackett, Alan J
中科院分区：
文献类型：
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作者：
Chiang, Tung-Chin;Koss, Brian;Tackett, Alan J
背景：紫外线照射引起的氧化应激是黑色素瘤的驱动机制。氧化应激增加会导致 DNA 损伤和表观遗传失调。因此，我们探讨了低剂量的抗氧化剂萝卜硫素 (SFN) 与表观遗传药物 5-aza-2'-脱氧胞苷 (DAC) 组合是否可以减缓黑色素瘤细胞的生长。 SFN 是十字花科植物的天然生物活性产品，而 DAC 是 DNA 甲基转移酶抑制剂。方法：在 SFN 和 DAC 单独和联合治疗后测量黑色素瘤细胞生长特征、基因转录谱和组蛋白表观遗传修饰。结果：我们检测到 SFN 和 DAC 联合治疗后黑色素瘤细胞生长抑制和基因表达谱的特定变化，但没有观察到组蛋白表观遗传修饰的显着变化。关键免疫调节因子 C-C 基序配体 5 (CCL-5) 的基因转录失调已得到验证。结论：这些结果表明膳食抗氧化剂和 FDA 批准的表观遗传药物在控制黑色素瘤细胞生长方面具有潜在的组合作用。
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.