title: Inhibitory effects of kaempferol on the invasion of human breast carcinoma cells by downregulating the expression and activity of matrix metalloproteinase-9.
abstract: 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 Cδ (PKCδ) 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 PKCδ/MAPK/AP-1 cascade and subsequent MMP-9 expression and its activity. Therefore, kaempferol might act as a therapeutic potential candidate for cancer metastasis.
authors.affiliation: a Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical College, Tongshan Road 209#, 221004, Xuzhou, People's Republic of China.
authors.forename: Chenglin
authors.initials: C
authors.lastname: Li
authors.forename: Yuanwei
authors.initials: Y
authors.lastname: Zhao
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Yu
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.forename: Ziming
authors.initials: Z
authors.lastname: Zhao
authors.forename: Bei
authors.initials: B
authors.lastname: Zhang
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Yin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation; D005260:Female; D006801:Humans; D044949:Kaempferols / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D051745:Protein Kinase C-delta / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D044949:Kaempferols; D018808:Transcription Factor AP-1; C006552:kaempferol; D051745:Protein Kinase C-delta; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: MAPK; PKCδ; invasion; kaempferol; kaempférol