Resveratrol induces MMP-9 and cell migration via the p38 kinase and PI-3K pathways in HT1080 human fibrosarcoma cells

Abstract

Abstract. 4', is a grape polyphenol present in various plants, food products, red wine and grapes. Resveratrol has anti-inflammatory, anticarcinogenic, anti-oxidant and anti-aging properties. Matrix metalloproteinases (MMPs) are key enzymes involved in the degradation of the extracellular matrix, and their expression may be regulated in cancer metastasis. In the present study, we aimed to evaluate the effect of resveratrol on MMPs and cell migration, and to understand the mechanism of action in HT1080 human fibrosarcoma cells. We found that resveratrol inhibited HT1080 cell viability at various concentrations as detected by the MTT assay and FACS analysis. However, resveratrol dramatically increased the activation and expression of MMP-9 in a dose-and time-dependent manner, as determined by gelatin zymography assay and western blot analysis. We also discovered that resveratrol enhanced the migratory ability of HT1080 cells, as determined by the wound healing assay, and decreased the phosphorylation of p38 kinase. Moreover, the Akt kinase was inhibited by resveratrol in the HT1080 cells. The inhibition of p38 and Akt kinases with SB203580 and LY294002 further increased resveratrol-induced MMP-9 as well as cell migration in the HT1080 cells. Our results suggest that resveratrol regulates MMP-9 and migratory abilities through the p38 kinase and PI-3K pathways in HT1080 human fibrosarcoma cells.

PAD1 promotes epithelial-mesenchymal transition and metastasis in triple-negative breast cancer cells by regulating MEK1-ERK1/2-MMP2 signaling

“…One of the first steps of metastasis is the degradation of the basement membrane and stromal extracellular matrix (ECM), which form physical barriers to restrict cell movement [5,6]. During this process, matrix metalloproteinases (MMPs) are involved in the breakdown of the ECM components, thereby facilitating tumor progression and metastasis [4,7,8].…”

Targeting extracellular matrix remodeling in disease: Could resveratrol be a potential candidate?

“…83 Contrary to this, Gweon and Kim showed that treatment of HT1080 human fibrosarcoma cells with resveratrol 50 mM results in inhibition of p38 phosphorylation resulting in increased MMP-9 secretion. 42 One of the in vivo studies using streptozotocin-induced diabetic rats showed that resveratrol favorably shifts ERK1/2 and p38 MAPK activation. 84 In contrast to all the above observations, Jiao et al showed that treatment of glioblastoma-initiating cells with resveratrol although reduced Akt and mTOR phosphorylation, did not affect the phosphorylation of the ERK1/2, p38, and JNK pathways.…”

“…82 Contrary to the above finding, Gweon and Kim showed that treatment of HT1080 human fibrosarcoma cells with resveratrol (50 mM) for 24 h causes increased MMP-9 secretion due to inhibition of Akt phosphorylation. 42 Mitogen activated protein (MAP) kinase pathway. The MAP kinases are involved in the regulation of MMPs and are modulated by transcription factors.…”

“…40,41 In contrast, resveratrol caused a dose-dependent increased activation and expression of MMP-9 in HT1080 human fibrosarcoma cells. 42 Besides tumorigenesis and metastatic progression of cancer, MMPs also play a role in ECM remodeling in response to inflammation. Treatment of U937 cell line, a human promonocytic cell line, with PMA (10 pmol/L -0.1 mmol/L) induces cell differentiation and increased MMP-9 production that mimics inflammatory conditions.…”

Hexane and Chloroform Fractions of Laetiporus sulphrueus var. miniatus Inhibit Thrombin-treated Matrix Metalloproteinase- 2/9 Expression in Human Oral Squamous Carcinoma YD-10B Cells

“…Thus, at uncontrolled levels, ROS can cause a wide variety of human disorders and diseases, including cancers [11,12]. Several studies indicate that antioxidants exhibit anti-invasive activity against cancer cells by inhibiting MMP expression [13,14].…”