title: Gallic acid suppresses the migration and invasion of PC-3 human prostate cancer cells via inhibition of matrix metalloproteinase-2 and -9 signaling pathways.
abstract: Epidemiological studies have demonstrated that a natural diet or consumption of fruits or vegetables can decrease the risk of cancer development. Cancer cells can migrate to and invade other organs or tissues that cause more difficulty to treat them and this also results in the need for treatments targeting multiple cellular pathways. Gallic acid (GA) has been demonstrated to possess multiple biological activities including anticancer function. However, no report exist on GA inhibited invasion and migration of human prostate cancer cells. We investigated the effects of migration and invasion in GA-treated PC-3 human prostate cancer cells with a series of in vitro experiments. Boyden chamber transwell assay was used to examine the migration and invasion of PC-3 cells. Western blotting, real-time PCR and gelatin zymography were used for determining the protein levels, gene expression and enzyme activities of matrix metalloproteinase-2 (MMP-2) and -9 in vitro. Results indicated that GA inhibited the invasion and migration of PC-3 cells and these effects are dose-dependent. GA inhibited the protein levels of MMP-2 and -9, son of sevenless homolog 1 (SOS1), growth factor receptor-bound protein 2 (GRB2), protein kinase C (PKC) and nuclear factor-κ B (NF-κB) p65, c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), p38, p-AKT (Thr308) and p-AKT (Ser473), but it promoted the levels of phosphatidylinositol 3-kinase (PI3K) and AKT in PC-3 cells. GA also reduced the enzyme activities of MMP-2 and -9 in the examined cells. Moreover, the down-regulation of focal adhesion kinase (FAK) and Ras homolog gene family, member A (Rho A) mRNA expression levels, and up-regulation of the tissue inhibitor of metalloproteinase-1 (TIMP1) gene levels occurred in GA-treated PC-3 cells after 24 h treatment. Based on these observations, we suggest that GA might modulate through blocking the p38, JNK, PKC and PI3K/AKT signaling pathways and reducing the NF-κB protein level, resulting in the inhibition of MMP-2 and -9 of PC-3 human prostate cancer cells.
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, School of Pharmacy, China Medical University, Taichung 404, Taiwan, ROC.
authors.forename: Kuo-Ching
authors.initials: KC
authors.lastname: Liu
authors.forename: An-Cheng
authors.initials: AC
authors.lastname: Huang
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Wu
authors.forename: Hui-Yi
authors.initials: HY
authors.lastname: Lin
authors.forename: Fu-Shin
authors.initials: FS
authors.lastname: Chueh
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.forename: Chi-Cheng
authors.initials: CC
authors.lastname: Lu
authors.forename: Jo-Hua
authors.initials: JH
authors.lastname: Chiang
authors.forename: Menghsiao
authors.initials: M
authors.lastname: Meng
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D004305:Dose-Response Relationship, Drug; D005707:Gallic Acid / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000378:metabolism*; D015398:Signal Transduction; D014945:Wound Healing
chemical_list: D005707:Gallic Acid; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9