title: Gallic acid-capped gold nanoparticles inhibit EGF-induced MMP-9 expression through suppression of p300 stabilization and NFκB/c-Jun activation in breast cancer MDA-MB-231 cells.
abstract: Triple-negative breast cancers (TNBCs) are highly invasive and have a higher rate of distant metastasis. Matrix metalloproteinase-9 (MMP-9) plays a crucial role in EGF/EGFR-mediated malignant progression and metastasis of TNBCs. Various studies have revealed that treatment with gallic acid down-regulates MMP-9 expression in cancer cells, and that conjugation of phytochemical compounds with gold nanoparticles (AuNPs) increases the anti-tumor activity of the phytochemical compounds. Thus, the effect of gallic acid-capped AuNPs (GA-AuNPs) on MMP-9 expression in EGF-treated TNBC MDA-MB-231 cells was analyzed in the present study. The so-called green synthesis of AuNPs by means of gallic acid was performed at pH10, and the resulting GA-AuNPs had spherical shape with an average diameter of approximately 50nm. GA-AuNPs notably suppressed migration and invasion of EGF-treated cells, and inhibited EGF-induced MMP-9 up-regulation. GA-AuNPs abrogated EGF-induced Akt/p65 and ERK/c-Jun phosphorylation, leading to down-regulation of MMP-9 mRNA and protein expression in EGF-treated cells. Meanwhile, EGF-induced p300 stabilization was found to be involved in MMP-9 expression, whereas GA-AuNPs inhibited the EGF-promoted stability of the p300 protein. Although GA-AuNPs and gallic acid suppressed EGF-induced MMP-9 up-regulation via the same signaling pathway, the effective concentration of gallic acid was approximately 100-fold higher than that of GA-AuNPs for inhibition of MMP-9 expression in EGF-treated cells to a similar extent. Collectively, our data indicate that, in comparison with gallic acid, GA-AuNPs have a superior ability to inhibit EGF/EGFR-mediated MMP-9 expression in TNBC MDA-MB-231 cells. Our findings also point to a way to improve the anti-tumor activity of gallic acid.
authors.affiliation: Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
authors.forename: Ying-Jung
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
authors.forename: Yuan-Chin
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Huang
authors.affiliation: Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan; Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan. Electronic address: lschang@mail.nsysu.edu.tw.
authors.forename: Long-Sen
authors.initials: LS
authors.lastname: Chang
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D005707:Gallic Acid / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D053768:Metal Nanoparticles / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D016328:NF-kappa B / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D005707:Gallic Acid; D006046:Gold; D050880:p300-CBP Transcription Factors; D020780:Matrix Metalloproteinase 9
keywords: Breast cancer; EGF; Gallic acid-capped gold nanoparticles; MMP-9; NFκB/AP-1; p300