Inhibition of the STAT3 Signaling Pathway Contributes to Apigenin-mediated Anti-metastatic Effect in Melanoma

Overview

Journal Sci Rep

Specialty Science

Date 2016 Feb 26

PMID 26911838

Citations 61

Authors

Hui-Hui Cao

Jian-Hong Chu

Hiu-Yee Kwan

Tao Su

Hua Yu

Chi-Yan Cheng

Xiu-Qiong Fu

Hui Guo

Ting Li

Anfernee Kai-Wing Tse

Gui-Xin Chou

Huan-Biao Mo

Zhi-Ling Yu

Affiliations

Soon will be listed here.

Abstract

Signal transducer and activator of transcription 3 (STAT3) signaling is constantly activated in human melanoma, and promotes melanoma metastasis. The dietary flavonoid apigenin is a bioactive compound that possesses low toxicity and exerts anti-metastatic activity in melanoma. However, the anti-metastasis mechanism of apigenin has not been fully elucidated. In the present study, we showed that apigenin suppressed murine melanoma B16F10 cell lung metastasis in mice, and inhibited cell migration and invasion in human and murine melanoma cells. Further study indicated that apigenin effectively suppressed STAT3 phosphorylation, decreased STAT3 nuclear localization and inhibited STAT3 transcriptional activity. Apigenin also down-regulated STAT3 target genes MMP-2, MMP-9, VEGF and Twist1, which are involved in cell migration and invasion. More importantly, overexpression of STAT3 or Twist1 partially reversed apigenin-impaired cell migration and invasion. Our data not only reveal a novel anti-metastasis mechanism of apigenin but also support the notion that STAT3 is an attractive and promising target for melanoma treatment.

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