title: Gallic acid inhibits the migration and invasion of A375.S2 human melanoma cells through the inhibition of matrix metalloproteinase-2 and Ras.
abstract: Melanoma is one of the most common cancers worldwide and its incidence has been increasing over the past few decades. Gallic acid (GA) can inhibit the growth of human cancer cells in vitro and in vivo. However, there is no available information to address the effects of GA on migration and invasion of human skin cancer cells. Matrix metalloproteinases (MMPs), zinc-dependent proteolytic enzymes, play an important role in the invasion, metastasis, and angiogenesis of cancer cells. Therefore, MMPs are one of the targets for agents to suppress and that could inhibit the migration and invasion of cancer cells. GA affected the viable A375.S2 cells by propidium iodide exclusion and flow cytometric analysis. Cell migration and invasion were investigated by Boyden chamber assay and we also determined the levels of protein and mRNA expression cell migration and invasion by gelatin zymography, western blotting, and real-time PCR assays. In this study, we examined the influence of GA on the protein levels and gene expression of MMP-2 and MMP-9 and in-vitro migration and invasiveness of human melanoma cells. GA decreases the MMPs and associated signal pathway protein and MMPs mRNA levels in A375.S2 human melanoma cells. Our findings suggest that GA has antimetastatic potential by decreasing invasiveness of cancer cells. Moreover, this action of GA was involved in the Ras, p-ERK signaling pathways resulting in inhibition of MMP-2 in A375.S2 human melanoma cells. These data, therefore, provide evidence for the role of GA as a potential cancer chemotherapeutic agent, which can markedly inhibit the invasive capacity of melanoma cells.
authors: School of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors: Chyi
authors: C
authors: Lo
authors: Tung-Yuan
authors: TY
authors: Lai
authors: Jai-Sing
authors: JS
authors: Yang
authors: Jen-Hung
authors: JH
authors: Yang
authors: Yi-Shih
authors: YS
authors: Ma
authors: Shu-Wen
authors: SW
authors: Weng
authors: Hui-Yi
authors: HY
authors: Lin
authors: Hung-Yi
authors: HY
authors: Chen
authors: Jaung-Geng
authors: JG
authors: Lin
authors: Jing-Gung
authors: JG
authors: Chung
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D054443:Cell Migration Assays; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D005707:Gallic Acid / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008545:Melanoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D013997:Time Factors; D018631:ras Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D005707:Gallic Acid; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D018631:ras Proteins