15d-PGJ2 inhibits NF-kB and AP-1-mediated MMP-9 expression and invasion of breast cancer cell by means of a heme oxygenase-1-dependent mechanism
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Activation of peroxisome proliferator-activated receptor (PPAR) serves as a key factor in the proliferation and invasion of breast cancer cells and is a potential therapeutic target for breast cancer. However, the mechanisms underlying this effect remain largely unknown. Heme oxygenase-1 (HO-1) is induced and overexpressed in various cancers and is associated with features of tumor aggressiveness. Recent studies have shown that HO-1 is a major downstream target of PPAR. In this study, we investigated the effects of induction of HO-1 by PPAR on TPAinduced MMP-9 expression and cell invasion using MCF-7 breast cancer cells. TPA treatment increased NF-B /AP-1 DNA binding as well as MMP-9 expression. These effects were significantly blocked by 15d-PGJ2, a natural PPAR ligand. 15d-PGJ2 induced HO-1 expression in a dose-dependent manner. Interestingly, HO-1 siRNA significantly attenuated the inhibition of TPA-induced MMP-9 protein expression and cell invasion by 15d-PGJ2. These results suggest that 15d-PGJ2 inhibits TPA-induced MMP- 9 expression and invasion of MCF-7 cells by means of a heme oxygenase-1-dependent mechanism. Therefore, PPAR/HO-1 signaling- pathway inhibition may be beneficial for prevention and treatment of breast cancer.
Abstract
Activation of peroxisome proliferator-activated receptor (PPAR) serves as a key factor in the proliferation and invasion of breast cancer cells and is a potential therapeutic target for breast cancer. However, the mechanisms underlying this effect remain largely unknown. Heme oxygenase-1 (HO-1) is induced and overexpressed in various cancers and is associated with features of tumor aggressiveness. Recent studies have shown that HO-1 is a major downstream target of PPAR. In this study, we investigated the effects of induction of HO-1 by PPAR on TPAinduced MMP-9 expression and cell invasion using MCF-7 breast cancer cells. TPA treatment increased NF-B /AP-1 DNA binding as well as MMP-9 expression. These effects were significantly blocked by 15d-PGJ2, a natural PPAR ligand. 15d-PGJ2 induced HO-1 expression in a dose-dependent manner. Interestingly, HO-1 siRNA significantly attenuated the inhibition of TPA-induced MMP-9 protein expression and cell invasion by 15d-PGJ2. These results suggest that 15d-PGJ2 inhibits TPA-induced MMP- 9 expression and invasion of MCF-7 cells by means of a heme oxygenase-1-dependent mechanism. Therefore, PPAR/HO-1 signaling- pathway inhibition may be beneficial for prevention and treatment of breast cancer.
참고문헌 (24)
- Jablonska-Trypuc A, "Matrix metalloproteinases(MMPs), the main extracellular matrix(ECM)enzymes in collagen degradation, as a target for anticancer drugs", J Enzy Inhi Med Chem, 31, pp.177~183 (2016)
- Pellikainen JM, "Expression of matrix metalloproteinase(MMP)-2 and MMP-9 in breast cancer with a special reference to activator protein-2, HER2, and prognosis", Clin Cancer Res, 10, pp.7621~7628 (2004)
- Kohrmann A, "Expression of matrix metalloproteinases(MMPs)in primary human breast cancer and breast cancer cell lines : New findings and review of the literature", BMC Cancer, 9, pp.188~ (2009)
- Ono Y, "Phorbol ester binding to protein kinase C requires a cysteine-rich zincfinger-like sequence", Proc Natl Acad Sci U S A, 86, pp.4868~4871 (1989)
- Gould CM, "The life and death of protein kinase C", Curr Drug Targets, 9, pp.614~625 (2008)
- Su Z, "Tumor promoter TPA activates Wnt", beta-catenin signaling in a casein kinase 1-dependent manner, 2018, pp.115, E7522~E7531
- Kim HJ, "Curcumin suppresses migration and proliferation of Hep3B hepatocarcinoma cells through inhibition of the Wnt signaling pathway", Mol Med Rep, 8, pp.282~286 (2013)
- Diradourian C, "Phosphorylation of PPARs : from molecular characterization to physiological relevance", Biochimie, 87, pp.33~38 (2005)
- Wang X, "PPARgamma maintains ERBB2-positive breast cancer stem cells", Oncogene, 32, pp.5512~5521 (2013)
- Robbins GT, "PPAR gamma, bioactive lipids, and cancer progression", Front Biosci (Landmark Ed), 17, pp.1816~1834 (2012)
- Kourtidis A, "Peroxisome proliferator-activated receptor-gamma protects ERBB2-positive breast cancer cells from palmitate toxicity", Breast Cancer Res, 11, pp.R16~ (2009)
- Srivastava N, "Inhibition of cancer cell proliferation by PPARgamma is mediated by a metabolic switch that increases reactive oxygen species levels", Cell Metab, 20, pp.650~661 (2014)
- Tsubaki M, "Pioglitazone inhibits cancer cell growth through STAT3 inhibition and enhanced AIF expression via a PPARgamma-independent pathway", J Cell Physiol, 233, pp.3638~3647 (2018)
- Liu H, "PPARgamma ligands and ATRA inhibit the invasion of human breast cancer cells in vitro", Breast Cancer Res Treat, 79, pp.63~74 (2003)
- Lin CW, "Heme oxygenase-1 inhibits breast cancer invasion via suppressing the expression of matrix metalloproteinase-9", Mol Cancer Ther, 7, pp.1195~1206 (2008)
- Yokoo T, "Dual regulation of IL-1beta-mediated matrix metalloproteinase-9 expression in mesangial cells by NF-kappa B and AP-1", Am J Physiol, 270, pp.F123~130 (1996)
- Jung Hyun Park, "Melittin Suppresses PMA-Induced Tumor Cell Invasion by Inhibiting NF-κB and AP-1-Dependent MMP-9 Expression", Molecules and Cells, 29(2), pp.209~215 (2010), 한국분자세포생물학회
- Maines MD, "Heme oxygenase : function, multiplicity, regulatory mechanisms, and clinical applications", FASEB J, 2, pp.2557~2568 (1988)
- Wu ML, "Heme oxygenase-1 in inflammation and cardiovascular disease", Am J Cardiovasc Dis, 1, pp.150~158 (2011)
- 이하나, "Heme Oxygenase-1 Determines the Differential Response of Breast Cancer and Normal Cells to Piperlongumine", Molecules and Cells, 38(4), pp.327~335 (2015), 한국분자세포생물학회
- Lee WY, "The induction of heme oxygenase-1 suppresses heat shock protein 90 and the proliferation of human breast cancer cells through its byproduct carbon monoxide", Toxicol Appl Pharmacol, 274, pp.55~62 (2014)
- Kronke G, "Expression of heme oxygenase-1 in human vascular cells is regulated by peroxisome proliferator-activated receptors", Arterioscler Thromb Vasc Biol, 27, pp.1276~1282 (2007)
- 박소연, "HO-1 Induced by Cilostazol Protects Against TNF-α-Associated Cytotoxicity via a PPAR-γ-Dependent Pathway in Human Endothelial Cells", The Korean Journal of Physiology & Pharmacology, 15(2), pp.83~88 (2011), 대한약리학회
- Vanella L, "HO-1expression increases mesenchymal stem cell-derived osteoblasts but decreases adipocyte lineage", Bone, 46, pp.236~243 (2010)