Inhibition of the STAT3 signaling pathway contributes to apigenin-mediated anti-metastatic effect in melanoma

Hui Hui Cao, Jian Hong Chu, Hiu Yee Kwan, Tao Su, Hua Yu, Chi Yan Cheng, Xiuqiong Fu, Hui Guo, Ting Li, Anfernee K W Tse, Gui Xin Chou, Huan Biao Mo, Zhiling Yu*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

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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.

Original languageEnglish
Article number21731
Number of pages12
JournalScientific Reports
Publication statusPublished - 25 Feb 2016

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