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Licochalcone A, a Polyphenol Present in Licorice, Suppresses UV-Induced COX-2 Expression by Targeting PI3K, MEK1, and B-Raf

Licorice is a traditional botanical medicine, and has historically been commonly prescribed in Asia to treat various diseases. Glycyrrhizin (Gc), a triterpene compound, is the most abundant phytochemical constituent of licorice. However, high intake or long-term consumption of Gc has been associated...

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Autores principales: Song, Nu Ry, Kim, Jong-Eun, Park, Jun Seong, Kim, Jong Rhan, Kang, Heerim, Lee, Eunjung, Kang, Young-Gyu, Son, Joe Eun, Seo, Sang Gwon, Heo, Yong Seok, Lee, Ki Won
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394430/
https://www.ncbi.nlm.nih.gov/pubmed/25710724
http://dx.doi.org/10.3390/ijms16034453
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author Song, Nu Ry
Kim, Jong-Eun
Park, Jun Seong
Kim, Jong Rhan
Kang, Heerim
Lee, Eunjung
Kang, Young-Gyu
Son, Joe Eun
Seo, Sang Gwon
Heo, Yong Seok
Lee, Ki Won
author_facet Song, Nu Ry
Kim, Jong-Eun
Park, Jun Seong
Kim, Jong Rhan
Kang, Heerim
Lee, Eunjung
Kang, Young-Gyu
Son, Joe Eun
Seo, Sang Gwon
Heo, Yong Seok
Lee, Ki Won
author_sort Song, Nu Ry
collection PubMed
description Licorice is a traditional botanical medicine, and has historically been commonly prescribed in Asia to treat various diseases. Glycyrrhizin (Gc), a triterpene compound, is the most abundant phytochemical constituent of licorice. However, high intake or long-term consumption of Gc has been associated with a number of side effects, including hypertension. However, the presence of alternative bioactive compounds in licorice with anti-carcinogenic effects has long been suspected. Licochalcone A (LicoA) is a prominent member of the chalcone family and can be isolated from licorice root. To date, there have been no reported studies on the suppressive effect of LicoA against solar ultraviolet (sUV)-induced cyclooxygenase (COX)-2 expression and the potential molecular mechanisms involved. Here, we show that LicoA, a major chalcone compound of licorice, effectively inhibits sUV-induced COX-2 expression and prostaglandin E2 PGE(2) generation through the inhibition of activator protein 1 AP-1 transcriptional activity, with an effect that is notably more potent than Gc. Western blotting analysis shows that LicoA suppresses sUV-induced phosphorylation of Akt/ mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinases (ERK)1/2/p90 ribosomal protein S6 kinase (RSK) in HaCaT cells. Moreover, LicoA directly suppresses the activity of phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase kinase (MEK)1, and B-Raf, but not Raf-1 in cell-free assays, indicating that PI3K, MEK1, and B-Raf are direct molecular targets of LicoA. We also found that LicoA binds to PI3K and B-Raf in an ATP-competitive manner, although LicoA does not appear to compete with ATP for binding with MEK1. Collectively, these results provide insight into the biological action of LicoA, which may have potential for development as a skin cancer chemopreventive agent.
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spelling pubmed-43944302015-05-21 Licochalcone A, a Polyphenol Present in Licorice, Suppresses UV-Induced COX-2 Expression by Targeting PI3K, MEK1, and B-Raf Song, Nu Ry Kim, Jong-Eun Park, Jun Seong Kim, Jong Rhan Kang, Heerim Lee, Eunjung Kang, Young-Gyu Son, Joe Eun Seo, Sang Gwon Heo, Yong Seok Lee, Ki Won Int J Mol Sci Article Licorice is a traditional botanical medicine, and has historically been commonly prescribed in Asia to treat various diseases. Glycyrrhizin (Gc), a triterpene compound, is the most abundant phytochemical constituent of licorice. However, high intake or long-term consumption of Gc has been associated with a number of side effects, including hypertension. However, the presence of alternative bioactive compounds in licorice with anti-carcinogenic effects has long been suspected. Licochalcone A (LicoA) is a prominent member of the chalcone family and can be isolated from licorice root. To date, there have been no reported studies on the suppressive effect of LicoA against solar ultraviolet (sUV)-induced cyclooxygenase (COX)-2 expression and the potential molecular mechanisms involved. Here, we show that LicoA, a major chalcone compound of licorice, effectively inhibits sUV-induced COX-2 expression and prostaglandin E2 PGE(2) generation through the inhibition of activator protein 1 AP-1 transcriptional activity, with an effect that is notably more potent than Gc. Western blotting analysis shows that LicoA suppresses sUV-induced phosphorylation of Akt/ mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinases (ERK)1/2/p90 ribosomal protein S6 kinase (RSK) in HaCaT cells. Moreover, LicoA directly suppresses the activity of phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase kinase (MEK)1, and B-Raf, but not Raf-1 in cell-free assays, indicating that PI3K, MEK1, and B-Raf are direct molecular targets of LicoA. We also found that LicoA binds to PI3K and B-Raf in an ATP-competitive manner, although LicoA does not appear to compete with ATP for binding with MEK1. Collectively, these results provide insight into the biological action of LicoA, which may have potential for development as a skin cancer chemopreventive agent. MDPI 2015-02-20 /pmc/articles/PMC4394430/ /pubmed/25710724 http://dx.doi.org/10.3390/ijms16034453 Text en © 2015 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 license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Song, Nu Ry
Kim, Jong-Eun
Park, Jun Seong
Kim, Jong Rhan
Kang, Heerim
Lee, Eunjung
Kang, Young-Gyu
Son, Joe Eun
Seo, Sang Gwon
Heo, Yong Seok
Lee, Ki Won
Licochalcone A, a Polyphenol Present in Licorice, Suppresses UV-Induced COX-2 Expression by Targeting PI3K, MEK1, and B-Raf
title Licochalcone A, a Polyphenol Present in Licorice, Suppresses UV-Induced COX-2 Expression by Targeting PI3K, MEK1, and B-Raf
title_full Licochalcone A, a Polyphenol Present in Licorice, Suppresses UV-Induced COX-2 Expression by Targeting PI3K, MEK1, and B-Raf
title_fullStr Licochalcone A, a Polyphenol Present in Licorice, Suppresses UV-Induced COX-2 Expression by Targeting PI3K, MEK1, and B-Raf
title_full_unstemmed Licochalcone A, a Polyphenol Present in Licorice, Suppresses UV-Induced COX-2 Expression by Targeting PI3K, MEK1, and B-Raf
title_short Licochalcone A, a Polyphenol Present in Licorice, Suppresses UV-Induced COX-2 Expression by Targeting PI3K, MEK1, and B-Raf
title_sort licochalcone a, a polyphenol present in licorice, suppresses uv-induced cox-2 expression by targeting pi3k, mek1, and b-raf
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394430/
https://www.ncbi.nlm.nih.gov/pubmed/25710724
http://dx.doi.org/10.3390/ijms16034453
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