Journal
BIOCHEMISTRY AND CELL BIOLOGY
Volume 93, Issue 1, Pages 16-27Publisher
CANADIAN SCIENCE PUBLISHING
DOI: 10.1139/bcb-2014-0067
Keywords
kaempferol; invasion; MAPK; PKC delta
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Funding
- Natural Science Foundation of China [21205102, 81102381]
- Natural Science Foundation of Jiangsu province [BK20130220]
- China Postdoctoral Science Foundation [2013M541733]
- Jiangsu Planned Projects for Postdoctoral Research Funds [1301015B]
- Natural Science Foundation of the Jiangsu Higher Education Institutions of China [13KJB350007]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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Matrix metalloproteinases (MMPs) have been regarded as major critical molecules assisting tumor cells during metastasis, for excessive ECM (ECM) degradation, and cancer cell invasion. In the present study, in vitro and in vivo assays were employed to examine the inhibitory effects of kaempferol, a natural polyphenol of flavonoid family, on tumor metastasis. Data showed that kaempferol could inhibit adhesion, migration, and invasion of MDA-MB-231 human breast carcinoma cells. Moreover, kaempferol led to the reduced activity and expression of MMP-2 and MMP-9, which were detected by gelatin zymography, real-time PCR, and western blot analysis, respectively. Further elucidation of the mechanism revealed that kaempferol treatment inhibited the activation of transcription factor activator protein-1 (AP-1) and MAPK signaling pathway. Moreover, kaempferol repressed phorbol-12-myristate-13-acetate (PMA)-induced MMP-9 expression and activity through suppressing the translocation of protein kinase C delta (PKC delta) and MAPK signaling pathway. Our results also indicated that kaempferol could block the lung metastasis of B16F10 murine melanoma cells as well as the expression of MMP-9 in vivo. Taken together, these results demonstrated that kaempferol could inhibit cancer cell invasion through blocking the PKC delta/MAPK/AP-1 cascade and subsequent MMP-9 expression and its activity. Therefore, kaempferol might act as a therapeutic potential candidate for cancer metastasis.
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