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α-Mangostin, a Natural Agent, Enhances the Response of NRAS Mutant Melanoma to Retinoic Acid

BACKGROUND: The identification and use of novel compounds alone or in combination hold promise for the fight against NRAS mutant melanoma. MATERIAL/METHODS: We screened a kinase-specific inhibitor library through combining it with α-Mangostin in NRAS mutant melanoma cell line, and verified the enhan...

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Autores principales: Xia, Yun, Chen, Jing, Gong, Chongwen, Chen, Hongxiang, Sun, Jiaming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844330/
https://www.ncbi.nlm.nih.gov/pubmed/27104669
http://dx.doi.org/10.12659/MSM.898204
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author Xia, Yun
Chen, Jing
Gong, Chongwen
Chen, Hongxiang
Sun, Jiaming
author_facet Xia, Yun
Chen, Jing
Gong, Chongwen
Chen, Hongxiang
Sun, Jiaming
author_sort Xia, Yun
collection PubMed
description BACKGROUND: The identification and use of novel compounds alone or in combination hold promise for the fight against NRAS mutant melanoma. MATERIAL/METHODS: We screened a kinase-specific inhibitor library through combining it with α-Mangostin in NRAS mutant melanoma cell line, and verified the enhancing effect of α-Mangostin through inhibition of the tumorigenesis pathway. RESULTS: Within the kinase inhibitors, retinoic acid showed a significant synergistic effect with α-Mangostin. α-Mangostin also can reverse the drug resistance of retinoic acid in RARa siRNA-transduced sk-mel-2 cells. Colony assay, TUNEL staining, and the expressions of several apoptosis-related genes revealed that α-Mangostin enhanced the effect of retinoic acid-induced apoptosis. The combination treatment resulted in marked induction of ROS generation and inhibition of the AKT/S6 pathway. CONCLUSIONS: These results indicate that the combination of these novel natural agents with retinoid acid may be clinically effective in NRAS mutant melanoma.
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spelling pubmed-48443302016-05-05 α-Mangostin, a Natural Agent, Enhances the Response of NRAS Mutant Melanoma to Retinoic Acid Xia, Yun Chen, Jing Gong, Chongwen Chen, Hongxiang Sun, Jiaming Med Sci Monit Lab/In Vitro Research BACKGROUND: The identification and use of novel compounds alone or in combination hold promise for the fight against NRAS mutant melanoma. MATERIAL/METHODS: We screened a kinase-specific inhibitor library through combining it with α-Mangostin in NRAS mutant melanoma cell line, and verified the enhancing effect of α-Mangostin through inhibition of the tumorigenesis pathway. RESULTS: Within the kinase inhibitors, retinoic acid showed a significant synergistic effect with α-Mangostin. α-Mangostin also can reverse the drug resistance of retinoic acid in RARa siRNA-transduced sk-mel-2 cells. Colony assay, TUNEL staining, and the expressions of several apoptosis-related genes revealed that α-Mangostin enhanced the effect of retinoic acid-induced apoptosis. The combination treatment resulted in marked induction of ROS generation and inhibition of the AKT/S6 pathway. CONCLUSIONS: These results indicate that the combination of these novel natural agents with retinoid acid may be clinically effective in NRAS mutant melanoma. International Scientific Literature, Inc. 2016-04-22 /pmc/articles/PMC4844330/ /pubmed/27104669 http://dx.doi.org/10.12659/MSM.898204 Text en © Med Sci Monit, 2016 This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License
spellingShingle Lab/In Vitro Research
Xia, Yun
Chen, Jing
Gong, Chongwen
Chen, Hongxiang
Sun, Jiaming
α-Mangostin, a Natural Agent, Enhances the Response of NRAS Mutant Melanoma to Retinoic Acid
title α-Mangostin, a Natural Agent, Enhances the Response of NRAS Mutant Melanoma to Retinoic Acid
title_full α-Mangostin, a Natural Agent, Enhances the Response of NRAS Mutant Melanoma to Retinoic Acid
title_fullStr α-Mangostin, a Natural Agent, Enhances the Response of NRAS Mutant Melanoma to Retinoic Acid
title_full_unstemmed α-Mangostin, a Natural Agent, Enhances the Response of NRAS Mutant Melanoma to Retinoic Acid
title_short α-Mangostin, a Natural Agent, Enhances the Response of NRAS Mutant Melanoma to Retinoic Acid
title_sort α-mangostin, a natural agent, enhances the response of nras mutant melanoma to retinoic acid
topic Lab/In Vitro Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844330/
https://www.ncbi.nlm.nih.gov/pubmed/27104669
http://dx.doi.org/10.12659/MSM.898204
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