Inhibitory Effect of Dried Pomegranate Concentration Powder on Melanogenesis in B16F10 Melanoma Cells; Involvement of p38 and PKA Signaling Pathways

• Published in: International journal of molecular sciences Vol. 16; no. 10; pp. 24219 - 24242
• Main Authors: Kang, Su Jin, Choi, Beom Rak, Lee, Eun Kyoung, Kim, Seung Hee, Yi, Hae Yeon, Park, Hye Rim, Song, Chang Hyun, Lee, Young Joon, Ku, Sae Kwang
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13.10.2015; MDPI
• Subjects: alpha-MSH - pharmacology; Animals; anti-melanin; Antioxidants - pharmacology; Cell Line, Tumor; Cells; CREB-Binding Protein - metabolism; Cyclic AMP-Dependent Protein Kinases - metabolism; Flowers & plants; Free Radical Scavengers - pharmacology; Freeze Drying; Fruits; Glutathione Peroxidase - metabolism; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Kinases; Melanins - biosynthesis; Melanoma; Melanoma, Experimental - drug therapy; Mice; Microphthalmia-Associated Transcription Factor - metabolism; Monophenol Monooxygenase - metabolism; p38; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphatidylinositol 3-Kinase - metabolism; Phosphorylation - drug effects; Plant Preparations - pharmacology; pomegranate concentrate powder; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Punicaceae - metabolism; Signal transduction; whitening; whitening; anti-melanin; p38; pomegranate concentrate powder
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms161024219

Plants rich in antioxidant substances may be useful for preventing skin aging. Pomegranates, containing flavonoids and other polyphenolic compounds, are widely consumed due to their beneficial properties. We examined the underlying mechanisms of dried pomegranate concentrate powder (PCP) on melanin synthesis in B16F10 melanoma cells. The antioxidant effects of PCP were determined by measuring free radical scavenging capacity and transcript levels of antioxidant enzymes. To explore the inhibitory effects of PCP on melanin synthesis, we measured tyrosinase activity and melanin content in α-melanocyte stimulating hormone (α-MSH)-stimulated B16F10 cells. In addition, the levels of tyrosinase-related protein-1 (TRP-1), TRP-2, tyrosinase, and microphthalmia-associated transcription factor (MITF) expression were determined by Western blotting. Changes in the phosphorylation status of protein kinase A (PKA), cAMP response element-binding protein (CREB), mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3-kinase (PI3K), serine/threonine kinase Akt, and glycogen kinase 3β (GSK3β) were also examined. The free radical scavenging activity of PCP increased in a dose-dependent manner. In PCP-treated B16F10 cells, transcript levels of glutathione peroxidase-1 (GPx-1) were increased compared with α-MSH-stimulated cells. In addition, PCP led to the down-regulation of phospho-p38, phospho-PKA, phospho-CREB, phospho-GSK3β, MITF, and TRP-1 compared with α-MSH-stimulated B16F10 cells. We believe this effect may be associated with PCP activity, which leads to the inhibition of melanin production and tyrosinase activity. These results suggest that PCP decreases tyrosinase activity and melanin production via inactivation of the p38 and PKA signaling pathways, and subsequently decreases phosphorylation of CREB, MITF, and melanogenic enzymes. These observations provided new insights on the molecular mechanisms of the skin-whitening property of PCP.