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

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...

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Autores principales: Chiang, Tung-chin, Koss, Brian, Su, L. Joseph, Washam, Charity L., Byrum, Stephanie D., Storey, Aaron, Tackett, Alan J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789461/
https://www.ncbi.nlm.nih.gov/pubmed/31252639
http://dx.doi.org/10.3390/medicines6030071
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author Chiang, Tung-chin
Koss, Brian
Su, L. Joseph
Washam, Charity L.
Byrum, Stephanie D.
Storey, Aaron
Tackett, Alan J.
author_facet Chiang, Tung-chin
Koss, Brian
Su, L. Joseph
Washam, Charity L.
Byrum, Stephanie D.
Storey, Aaron
Tackett, Alan J.
author_sort Chiang, Tung-chin
collection PubMed
description 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.
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spelling pubmed-67894612019-10-16 Effect of Sulforaphane and 5-Aza-2’-Deoxycytidine on Melanoma Cell Growth Chiang, Tung-chin Koss, Brian Su, L. Joseph Washam, Charity L. Byrum, Stephanie D. Storey, Aaron Tackett, Alan J. Medicines (Basel) Article 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. MDPI 2019-06-27 /pmc/articles/PMC6789461/ /pubmed/31252639 http://dx.doi.org/10.3390/medicines6030071 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chiang, Tung-chin
Koss, Brian
Su, L. Joseph
Washam, Charity L.
Byrum, Stephanie D.
Storey, Aaron
Tackett, Alan J.
Effect of Sulforaphane and 5-Aza-2’-Deoxycytidine on Melanoma Cell Growth
title Effect of Sulforaphane and 5-Aza-2’-Deoxycytidine on Melanoma Cell Growth
title_full Effect of Sulforaphane and 5-Aza-2’-Deoxycytidine on Melanoma Cell Growth
title_fullStr Effect of Sulforaphane and 5-Aza-2’-Deoxycytidine on Melanoma Cell Growth
title_full_unstemmed Effect of Sulforaphane and 5-Aza-2’-Deoxycytidine on Melanoma Cell Growth
title_short Effect of Sulforaphane and 5-Aza-2’-Deoxycytidine on Melanoma Cell Growth
title_sort effect of sulforaphane and 5-aza-2’-deoxycytidine on melanoma cell growth
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789461/
https://www.ncbi.nlm.nih.gov/pubmed/31252639
http://dx.doi.org/10.3390/medicines6030071
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