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

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.

Licochalcones extracted from Glycyrrhiza inflata inhibit platelet aggregation accompanied by inhibition of COX-1 activity

“…Hence, licochalcone A is not a selective inhibitor for these COX isoforms compared with a COX-2-selective inhibitor such as celecoxib, the ratio of which is approximately 9.49 for ovine COX-1/ovine COX-2 and 600 for ovine COX-1/human COX-2 [17]. However, Song et al showed that licochalcone A did not cause inhibition of COX-2 activity in human keratinocytes [27], whereas we demonstrated that licochalcone A clearly blocked both COX isoforms in a concentration-dependent manner. The discrepancy between these results cannot be explained so far.…”

Licochalcone-E induces caspase-dependent death of human pharyngeal squamous carcinoma cells through the extrinsic and intrinsic apoptotic signaling pathways

“…Notably, the roots of licorice (Glycyrrhiza) have been used to treat inflammation, gastric ulcers and atherosclerosis, in folk and traditional herbal medicine in Eastern Asian countries, including Korea, Japan and China (30,31). Licorice root contains alkaloids, polysaccharides, and flavonoids (32).…”

Herbal medicine for hand–foot syndrome induced by fluoropyrimidines: A systematic review and meta‐analysis

“…Glycyrrhetinic acid markedly upregulated the activities of the antioxidant enzymes and increased the content of skin collagen, whereas it obviously downregulated the expression of inflammatory cytokines in vitro (Kong et al, ). Licochalcone A observably attenuated sUV‐induced COX‐2 expression in HaCaT human keratinocytes (Song et al, ). Licoricidin protected 3T3 fibroblasts against H 2 O 2 ‐induced oxidative stress (Kim, Xuan, & Park, ).…”