alexa Molecular Mechanisms Accounting For The Anti-melanoma Action Of Quercetin | 61731
ISSN: 2155-9554

Journal of Clinical & Experimental Dermatology Research
Open Access

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10th Asia-Pacific Dermatology Conference

Zhi-Ling Yu, Ting Li, Hui-Hui Cao, Xiu-Qiong Fu, Hui Guo, Pei-Li Zhu, Ya-Xi Li and Tao Su
Hong Kong Baptist University, Hong Kong
Posters & Accepted Abstracts: J Clin Exp Dermatol Res
DOI: 10.4172/2155-9554.C1.048
Abstract
Melanoma is the leading cause of skin cancer-related death. It is notorious for its propensity to metastasize. Constitutively activated signal transducer and activator of transcription 3 (STAT3) plays a critical role in melanoma development. c-Met is a receptor tyrosine kinase that plays a key role in the growth, metastasis and angiogenesis of melanoma cells. HGF (hepatocyte growth factor) is the solely known ligand of c-Met. Epithelial-mesenchymal transition (EMT) is proposed to be a crucial mechanism regulating the initial steps in metastatic progression and TGF-β is the best-studied inducer of EMT. The dietary flavonoid quercetin is a bioactive compound that possesses low toxicity and anticancer activities. Our results showed that quercetin was able to suppress the growth of human A375 melanoma tumor xenografts and lung metastasis of murine B16F10 cells in mouse models. In cultured melanoma cells, quercetin could induce apoptosis and inhibit proliferation, migration and invasion. These observations were associated with the inhibition of the STAT3, HGF/c-Met and TGF-β signaling pathways. Moreover, overexpression of a constitutively active variant of STAT3 (STAT3C) reduced the anti-proliferative effect of quercetin and overexpression of FAK or PAK significantly diminished the inhibitory effect of quercetin on melanoma cell migration. Quercetin also inhibited TGF-β1-induced EMT. These findings suggest that suppression of STAT3, HGF/c-Met and TGF-β signaling contribute to the anti-melanoma effects of quercetin and provide further pharmacological basis for developing quercetin as a melanoma chemopreventive/chemotherapeutic agent.
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