title: Inhibition of the STAT3 signaling pathway contributes to apigenin-mediated anti-metastatic effect in melanoma.
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.
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.|School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, P.R. China.
authors.forename: Hui-Hui
authors.initials: HH
authors.lastname: Cao
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Jian-Hong
authors.initials: JH
authors.lastname: Chu
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Hiu-Yee
authors.initials: HY
authors.lastname: Kwan
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Su
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Chi-Yan
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Xiu-Qiong
authors.initials: XQ
authors.lastname: Fu
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Anfernee Kai-Wing
authors.initials: AK
authors.lastname: Tse
authors.affiliation: The MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, P.R. China.
authors.forename: Gui-Xin
authors.initials: GX
authors.lastname: Chou
authors.affiliation: Department of Nutrition, Georgia State University, Georgia, USA.
authors.forename: Huan-Biao
authors.initials: HB
authors.lastname: Mo
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Yu
mesh_terms: D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D051879:Twist-Related Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D051879:Twist-Related Protein 1; D042461:Vascular Endothelial Growth Factor A; D047310:Apigenin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9