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Int J Mol Sci. 2015 Feb 20;16(3):4453-70. doi: 10.3390/ijms16034453.

Licochalcone A, a polyphenol present in licorice, suppresses UV-induced COX-2 expression by targeting PI3K, MEK1, and B-Raf.

Song NR1,2, Kim JE3,4, Park JS5, Kim JR3,4, Kang H6,7, Lee E8,9,10, Kang YG11, Son JE12,13, Seo SG14,15, Heo YS16, Lee KW17,18.

Author information

1
WCU Biomodulation Major, Center for Food and Bioconvergence, Department of Agricultural Biotechnology, Seoul National University, Seoul, 151-742, Korea. happynury@gmail.com.
2
Advanced Institute of Convergence Technology, Seoul National University, Suwon, 443-270, Korea. happynury@gmail.com.
3
WCU Biomodulation Major, Center for Food and Bioconvergence, Department of Agricultural Biotechnology, Seoul National University, Seoul, 151-742, Korea. allmendhubel@gmail.com.
4
Advanced Institute of Convergence Technology, Seoul National University, Suwon, 443-270, Korea. allmendhubel@gmail.com.
5
Skin Research Institute, Amorepacific R&D Center, Yongin, 446-829, Korea. superbody@amorepacific.com.
6
WCU Biomodulation Major, Center for Food and Bioconvergence, Department of Agricultural Biotechnology, Seoul National University, Seoul, 151-742, Korea. heeerim@gmail.com.
7
Advanced Institute of Convergence Technology, Seoul National University, Suwon, 443-270, Korea. heeerim@gmail.com.
8
WCU Biomodulation Major, Center for Food and Bioconvergence, Department of Agricultural Biotechnology, Seoul National University, Seoul, 151-742, Korea. thief28@snu.ac.kr.
9
Advanced Institute of Convergence Technology, Seoul National University, Suwon, 443-270, Korea. thief28@snu.ac.kr.
10
Traditional Alcoholic Beverage Research Team, Korea Food Research Institute, Seongnam 463-746, Korea. thief28@snu.ac.kr.
11
Skin Research Institute, Amorepacific R&D Center, Yongin, 446-829, Korea. kangyg82@amorepacific.com.
12
WCU Biomodulation Major, Center for Food and Bioconvergence, Department of Agricultural Biotechnology, Seoul National University, Seoul, 151-742, Korea. joe8601@gmail.com.
13
Advanced Institute of Convergence Technology, Seoul National University, Suwon, 443-270, Korea. joe8601@gmail.com.
14
WCU Biomodulation Major, Center for Food and Bioconvergence, Department of Agricultural Biotechnology, Seoul National University, Seoul, 151-742, Korea. seo0414@naver.com.
15
Advanced Institute of Convergence Technology, Seoul National University, Suwon, 443-270, Korea. seo0414@naver.com.
16
Department of Chemistry, Konkuk University, Seoul, 143-701, Korea. ysheo@konkuk.ac.kr.
17
WCU Biomodulation Major, Center for Food and Bioconvergence, Department of Agricultural Biotechnology, Seoul National University, Seoul, 151-742, Korea. kiwon@snu.ac.kr.
18
Advanced Institute of Convergence Technology, Seoul National University, Suwon, 443-270, Korea. kiwon@snu.ac.kr.

Abstract

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 PGE2 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.

PMID:
25710724
PMCID:
PMC4394430
DOI:
10.3390/ijms16034453
[Indexed for MEDLINE]
Free PMC Article

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