Peroxisome Proliferator-activated Receptor-γ As A Novel and Promising
Target For Treating Cancer Via Regulation of Inflammation: A Brief Review

S.      Yuvaraj; B.R.   Prashantha   Kumar

doi:10.2174/1389557521666210422112740

Abstract

Abstract: Peroxisome proliferator activated receptors (PPARs) are a group of nuclear receptors and the ligand-activated intracellular transcription factors that are known to play a key role in physiological processes such as cell metabolism, proliferation, differentiation, tissue remodeling, inflammation, and atherosclerosis. However, in the past two decades, many reports claim that PPARs also play an imperious role as a tumor suppressor. PPAR- gamma (PPARγ), one of the best-known from the family of PPARs, is known to express in colon, breast, bladder, lung, and prostate cancer cells. Its function in tumour cells includes the modulation of several pathways involved in multiplication and apoptosis. The ligands of PPARγ act by PPARγ dependent as well as independent pathways and are also found to regulate different inflammatory mediators and transcription factors in systemic inflammation and in tumor microenvironment. Both synthetic and natural ligands that are known to activate PPARγ, suppress the tumor cell growth and multiplication through the regulation of inflammatory pathways, as found out from different functional assays and animal studies. Cancer and inflammation are interconnected processes that are now being targeted to achieve tumor suppression by decreasing the risks and burden posed by cancer cells. Therefore, PPARγ can serve as a promising target for development of clinical drug molecule attenuating the proliferation of cancer cells. In this perspective, this mini review highlights the PPARγ as a potential target for drug development aiming for anti-inflammatory and thereby suppressing tumors.

Keywords: Peroxisome proliferator activated receptor gamma, thiazolidinediones, glitazones, inflammation, oncogenesis, antiinflammatory.

« Previous Next »

Graphical Abstract

[1] 
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin.,  2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593] 
[2] 
Ohshima, H.; Tatemichi, M.; Sawa, T. Chemical basis of inflammation-induced carcinogenesis. Arch. Biochem. Biophys.,  2003, 417(1), 3-11.
[http://dx.doi.org/10.1016/S0003-9861(03)00283-2] [PMID: 12921773] 
[3] 
Balkwill, F.; Mantovani, A. Inflammation and cancer: back to Virchow? Lancet,  2001, 357(9255), 539-545.
[http://dx.doi.org/10.1016/S0140-6736(00)04046-0] [PMID: 11229684] 
[4] 
Mantovani, A.; Allavena, P.; Sica, A.; Balkwill, F. Cancer-related inflammation. Nature,  2008, 454(7203), 436-444.
[http://dx.doi.org/10.1038/nature07205] [PMID: 18650914] 
[5] 
Loo, S.W.; Pui, T-S. Cytokine and Cancer Biomarkers Detection: The Dawn of Electrochemical Paper-Based Biosensor. Sensors (Basel),  2020, 20(7), 20.
[http://dx.doi.org/10.3390/s20071854] [PMID: 32230808] 
[6] 
Rayburn, E.R.; Ezell, S.J.; Zhang, R. Anti-Inflammatory Agents for Cancer Therapy. Mol. Cell. Pharmacol.,  2009, 1(1), 29-43.
[http://dx.doi.org/10.4255/mcpharmacol.09.05] [PMID: 20333321] 
[7] 
Nikolaou, M.; Pavlopoulou, A.; Georgakilas, A.G.; Kyrodimos, E. The challenge of drug resistance in cancer treatment: a current overview. Clin. Exp. Metastasis,  2018, 35(4), 309-318.
[http://dx.doi.org/10.1007/s10585-018-9903-0] [PMID: 29799080] 
[8] 
Zhao, L.; Hu, H.; Gustafsson, J-Å.; Zhou, S. Nuclear Receptors in Cancer Inflammation and Immunity. Trends Immunol.,  2020, 41(2), 172-185.
[http://dx.doi.org/10.1016/j.it.2019.12.006] [PMID: 31982345] 
[9] 
Peters, J.M.; Shah, Y.M.; Gonzalez, F.J. The role of peroxisome proliferator-activated receptors in carcinogenesis and chemoprevention. Nat. Rev. Cancer,  2012, 12(3), 181-195.
[http://dx.doi.org/10.1038/nrc3214] [PMID: 22318237] 
[10] 
Moraes, L.A.; Piqueras, L.; Bishop-Bailey, D. Peroxisome proliferator-activated receptors and inflammation. Pharmacol. Ther.,  2006, 110(3), 371-385.
[http://dx.doi.org/10.1016/j.pharmthera.2005.08.007] [PMID: 16168490] 
[11] 
Koeffler, H.P. Peroxisome proliferator-activated receptor γ and cancers. Clin. Cancer Res.,  2003, 9(1), 1-9.
[PMID: 12538445] 
[12] 
Straus, D.S.; Glass, C.K. Anti-inflammatory actions of PPAR ligands: new insights on cellular and molecular mechanisms. Trends Immunol.,  2007, 28(12), 551-558.
[http://dx.doi.org/10.1016/j.it.2007.09.003] [PMID: 17981503] 
[13] 
Daynes, R.A.; Jones, D.C. Emerging roles of PPARs in inflammation and immunity. Nat. Rev. Immunol.,  2002, 2(10), 748-759.
[http://dx.doi.org/10.1038/nri912] [PMID: 12360213] 
[14] 
Tontonoz, P.; Spiegelman, B.M. Fat and beyond: The diverse biology of PPARgamma. Annu. Rev. Biochem.,  2008, 77, 289-312.
[http://dx.doi.org/10.1146/annurev.biochem.77.061307.091829] [PMID: 18518822] 
[15] 
Lawrence, T.; Willoughby, D.A.; Gilroy, D.W. Anti-inflammatory lipid mediators and insights into the resolution of inflammation. Nat. Rev. Immunol.,  2002, 2(10), 787-795.
[http://dx.doi.org/10.1038/nri915] [PMID: 12360216] 
[16] 
Huang, T.H.W.; Kota, B.P.; Razmovski, V.; Roufogalis, B.D. Herbal or natural medicines as modulators of peroxisome proliferator-activated receptors and related nuclear receptors for therapy of metabolic syndrome. Basic Clin. Pharmacol. Toxicol.,  2005, 96(1), 3-14.
[http://dx.doi.org/10.1111/j.1742-7843.2005.pto960102.x] [PMID: 15667590] 
[17] 
Monsalve, F.A.; Pyarasani, R.D.; Delgado-Lopez, F.; Moore-Carrasco, R. Peroxisome proliferator-activated receptor targets for the treatment of metabolic diseases. Mediators Inflamm.,  2013, 2013, 549627.
[http://dx.doi.org/10.1155/2013/549627] [PMID: 23781121] 
[18] 
Jaradat, M.S.; Wongsud, B.; Phornchirasilp, S.; Rangwala, S.M.; Shams, G.; Sutton, M.; Romstedt, K.J.; Noonan, D.J.; Feller, D.R. Activation of peroxisome proliferator-activated receptor isoforms and inhibition of prostaglandin H(2) synthases by ibuprofen, naproxen, and indomethacin. Biochem. Pharmacol.,  2001, 62(12), 1587-1595.
[http://dx.doi.org/10.1016/S0006-2952(01)00822-X] [PMID: 11755111] 
[19] 
Leuti, A.; Fazio, D.; Fava, M.; Piccoli, A.; Oddi, S.; Maccarrone, M. Bioactive lipids, inflammation and chronic diseases. Adv. Drug Deliv. Rev.,  2020, 159, 133-169.
[http://dx.doi.org/10.1016/j.addr.2020.06.028] [PMID: 32628989] 
[20] 
van Kranen, H.J.; Siezen, C.L.E. Arachidonic Acid Pathway.Encyclopedia of Cancer; Schwab, M., Ed.; Springer: Berlin, Heidelberg, 2016, pp. 1-6.
[21] 
Piotrowski, I.; Kulcenty, K.; Suchorska, W. Interplay between inflammation and cancer. Rep. Pract. Oncol. Radiother.,  2020, 25(3), 422-427.
[http://dx.doi.org/10.1016/j.rpor.2020.04.004] [PMID: 32372882] 
[22] 
Issemann, I.; Green, S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature,  1990, 347(6294), 645-650.
[http://dx.doi.org/10.1038/347645a0] [PMID: 2129546] 
[23] 
Lalwani, N.D.; Alvares, K.; Reddy, M.K.; Reddy, M.N.; Parikh, I.; Reddy, J.K. Peroxisome proliferator-binding protein: identification and partial characterization of nafenopin-, clofibric acid-, and ciprofibrate-binding proteins from rat liver. Proc. Natl. Acad. Sci. USA,  1987, 84(15), 5242-5246.
[http://dx.doi.org/10.1073/pnas.84.15.5242] [PMID: 3474650] 
[24] 
Schmidt, A.; Endo, N.; Rutledge, S.J.; Vogel, R.; Shinar, D.; Rodan, G.A. Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids. Mol. Endocrinol.,  1992, 6(10), 1634-1641.
[PMID: 1333051] 
[25] 
Dreyer, C.; Krey, G.; Keller, H.; Givel, F.; Helftenbein, G.; Wahli, W. Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors. Cell,  1992, 68(5), 879-887.
[http://dx.doi.org/10.1016/0092-8674(92)90031-7] [PMID: 1312391] 
[26] 
Desvergne, B.; Wahli, W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr. Rev.,  1999, 20(5), 649-688.
[PMID: 10529898] 
[27] 
Mandard, S.; Müller, M.; Kersten, S. Peroxisome proliferator-activated receptor alpha target genes. Cell. Mol. Life Sci.,  2004, 61(4), 393-416.
[http://dx.doi.org/10.1007/s00018-003-3216-3] [PMID: 14999402] 
[28] 
Neels, J.G.; Grimaldi, P.A. Physiological functions of peroxisome proliferator-activated receptor β. Physiol. Rev.,  2014, 94(3), 795-858.
[http://dx.doi.org/10.1152/physrev.00027.2013] [PMID: 24987006] 
[29] 
Han, L.; Shen, W-J.; Bittner, S.; Kraemer, F.B.; Azhar, S. PPARs: regulators of metabolism and as therapeutic targets in cardiovascular disease. Part II: PPAR-β/δ and PPAR-γ. Future Cardiol.,  2017, 13(3), 279-296.
[http://dx.doi.org/10.2217/fca-2017-0019] [PMID: 28581362] 
[30] 
Cariou, B.; Charbonnel, B.; Staels, B. Thiazolidinediones and PPARγ agonists: time for a reassessment. Trends Endocrinol. Metab.,  2012, 23(5), 205-215.
[http://dx.doi.org/10.1016/j.tem.2012.03.001] [PMID: 22513163] 
[31] 
Chen, Y.; Jimenez, A.R.; Medh, J.D. Identification and regulation of novel PPAR-gamma splice variants in human THP-1 macrophages. Biochim. Biophys. Acta,  2006, 1759(1-2), 32-43.
[http://dx.doi.org/10.1016/j.bbaexp.2006.01.005] [PMID: 16542739] 
[32] 
Sauer, S. Ligands for the Nuclear Peroxisome Proliferator-Activated Receptor Gamma. Trends Pharmacol. Sci.,  2015, 36(10), 688-704.
[http://dx.doi.org/10.1016/j.tips.2015.06.010] [PMID: 26435213] 
[33] 
Fajas, L.; Auboeuf, D.; Raspé, E.; Schoonjans, K.; Lefebvre, A.M.; Saladin, R.; Najib, J.; Laville, M.; Fruchart, J.C.; Deeb, S.; Vidal-Puig, A.; Flier, J.; Briggs, M.R.; Staels, B.; Vidal, H.; Auwerx, J. The organization, promoter analysis, and expression of the human PPARgamma gene. J. Biol. Chem.,  1997, 272(30), 18779-18789.
[http://dx.doi.org/10.1074/jbc.272.30.18779] [PMID: 9228052] 
[34] 
Mukherjee, R.; Jow, L.; Croston, G.E.; Paterniti, J.R. Jr Identification, characterization, and tissue distribution of human peroxisome proliferator-activated receptor (PPAR) isoforms PPARgamma2 versus PPARgamma1 and activation with retinoid X receptor agonists and antagonists. J. Biol. Chem.,  1997, 272(12), 8071-8076.
[http://dx.doi.org/10.1074/jbc.272.12.8071] [PMID: 9065481] 
[35] 
Willson, T.M.; Lambert, M.H.; Kliewer, S.A. Peroxisome proliferator-activated receptor gamma and metabolic disease. Annu. Rev. Biochem.,  2001, 70, 341-367.
[http://dx.doi.org/10.1146/annurev.biochem.70.1.341] [PMID: 11395411] 
[36] 
Kota, B.P.; Huang, T.H-W.; Roufogalis, B.D. An overview on biological mechanisms of PPARs. Pharmacol. Res.,  2005, 51(2), 85-94.
[http://dx.doi.org/10.1016/j.phrs.2004.07.012] [PMID: 15629253] 
[37] 
Michalik, L.; Auwerx, J.; Berger, J.P.; Chatterjee, V.K.; Glass, C.K.; Gonzalez, F.J.; Grimaldi, P.A.; Kadowaki, T.; Lazar, M.A.; O’Rahilly, S.; Palmer, C.N.A.; Plutzky, J.; Reddy, J.K.; Spiegelman, B.M.; Staels, B.; Wahli, W. International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacol. Rev.,  2006, 58(4), 726-741.
[http://dx.doi.org/10.1124/pr.58.4.5] [PMID: 17132851] 
[38] 
Harmon, G.S.; Lam, M.T.; Glass, C.K. PPARs and lipid ligands in inflammation and metabolism. Chem. Rev.,  2011, 111(10), 6321-6340.
[http://dx.doi.org/10.1021/cr2001355] [PMID: 21988241] 
[39] 
Yang, C.; Li, Q.; Li, Y. Targeting nuclear receptors with marine natural products. Mar. Drugs,  2014, 12(2), 601-635.
[http://dx.doi.org/10.3390/md12020601] [PMID: 24473166] 
[40] 
Soccio, R.E.; Chen, E.R.; Lazar, M.A. Thiazolidinediones and the promise of insulin sensitization in type 2 diabetes. Cell Metab.,  2014, 20(4), 573-591.
[http://dx.doi.org/10.1016/j.cmet.2014.08.005] [PMID: 25242225] 
[41] 
Burton, J.D.; Goldenberg, D.M.; Blumenthal, R.D. Potential of peroxisome proliferator-activated receptor gamma antagonist compounds as therapeutic agents for a wide range of cancer types. PPAR Res.,  2008, 2008, 494161.
[http://dx.doi.org/10.1155/2008/494161] [PMID: 18779871] 
[42] 
Pirat, C.; Farce, A.; Lebègue, N.; Renault, N.; Furman, C.; Millet, R.; Yous, S.; Speca, S.; Berthelot, P.; Desreumaux, P.; Chavatte, P. Targeting peroxisome proliferator-activated receptors (PPARs): development of modulators. J. Med. Chem.,  2012, 55(9), 4027-4061.
[http://dx.doi.org/10.1021/jm101360s] [PMID: 22260081] 
[43] 
Zhang, F.; Lavan, B.E.; Gregoire, F.M. Selective Modulators of PPAR-gamma Activity: Molecular Aspects Related to Obesity and Side-Effects. PPAR Res.,  2007, 2007, 32696.
[http://dx.doi.org/10.1155/2007/32696] [PMID: 17389769] 
[44] 
Penumetcha, M.; Santanam, N. Nutraceuticals as Ligands of PPARγ. PPAR Res.,  2012, 2012, 858352.
[http://dx.doi.org/10.1155/2012/858352] [PMID: 22792089] 
[45] 
Mueller, M.; Jungbauer, A. Culinary Plants, Herbs and Spices – A Rich Source of PPARγ Ligands. Food Chem.,  2009, 117, 660-667.
[http://dx.doi.org/10.1016/j.foodchem.2009.04.063] 
[46] 
Wang, L.; Waltenberger, B.; Pferschy-Wenzig, E-M.; Blunder, M.; Liu, X.; Malainer, C.; Blazevic, T.; Schwaiger, S.; Rollinger, J.M.; Heiss, E.H.; Schuster, D.; Kopp, B.; Bauer, R.; Stuppner, H.; Dirsch, V.M.; Atanasov, A.G. Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review. Biochem. Pharmacol.,  2014, 92(1), 73-89.
[http://dx.doi.org/10.1016/j.bcp.2014.07.018] [PMID: 25083916] 
[47] 
Feng, X.; Weng, D.; Zhou, F.; Owen, Y.D.; Qin, H.; Zhao, J. WenYu; Huang, Y.; Chen, J.; Fu, H.; Yang, N.; Chen, D.; Li, J.; Tan, R.; Shen, P. Activation of PPARγ by a Natural Flavonoid Modulator, Apigenin Ameliorates Obesity-Related Inflammation Via Regulation of Macrophage Polarization. EBioMedicine,  2016, 9, 61-76.
[http://dx.doi.org/10.1016/j.ebiom.2016.06.017] [PMID: 27374313] 
[48] 
Ma, Z.; Ji, W.; Fu, Q.; Ma, S. Formononetin inhibited the inflammation of LPS-induced acute lung injury in mice associated with induction of PPAR gamma expression. Inflammation,  2013, 36(6), 1560-1566.
[http://dx.doi.org/10.1007/s10753-013-9700-5] [PMID: 23907652] 
[49] 
Feige, J.N.; Gelman, L.; Michalik, L.; Desvergne, B.; Wahli, W. From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions. Prog. Lipid Res.,  2006, 45(2), 120-159.
[http://dx.doi.org/10.1016/j.plipres.2005.12.002] [PMID: 16476485] 
[50] 
Lemberger, T.; Desvergne, B.; Wahli, W. Peroxisome proliferator-activated receptors: a nuclear receptor signaling pathway in lipid physiology. Annu. Rev. Cell Dev. Biol.,  1996, 12, 335-363.
[http://dx.doi.org/10.1146/annurev.cellbio.12.1.335] [PMID: 8970730] 
[51] 
Yki-Järvinen, H. Thiazolidinediones. N. Engl. J. Med.,  2004, 351(11), 1106-1118.
[http://dx.doi.org/10.1056/NEJMra041001] [PMID: 15356308] 
[52] 
Varga, T.; Czimmerer, Z.; Nagy, L. PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation. Biochim. Biophys. Acta,  2011, 1812(8), 1007-1022.
[http://dx.doi.org/10.1016/j.bbadis.2011.02.014] [PMID: 21382489] 
[53] 
Chakraborty, C.; Sharma, A.R.; Sharma, G.; Lee, S-S. The Interplay among miRNAs, Major Cytokines, and Cancer-Related Inflammation. Mol. Ther. Nucleic Acids,  2020, 20, 606-620.
[http://dx.doi.org/10.1016/j.omtn.2020.04.002] [PMID: 32348938] 
[54] 
Cantini, G.; Lombardi, A.; Borgogni, E.; Francalanci, M.; Ceni, E. Degl’Innocenti, S.; Gelmini, S.; Poli, G.; Galli, A.; Serio, M.; Forti, G.; Luconi, M. Peroxisome-proliferator-activated receptor gamma (PPARgamma) is required for modulating endothelial inflammatory response through a nongenomic mechanism. Eur. J. Cell Biol.,  2010, 89(9), 645-653.
[http://dx.doi.org/10.1016/j.ejcb.2010.04.002] [PMID: 20537761] 
[55] 
Adachi, M.; Kurotani, R.; Morimura, K.; Shah, Y.; Sanford, M.; Madison, B.B.; Gumucio, D.L.; Marin, H.E.; Peters, J.M.; Young, H.A.; Gonzalez, F.J. Peroxisome proliferator activated receptor γ in colonic epithelial cells protects against experimental inflammatory bowel disease. Gut,  2006, 55(8), 1104-1113.
[http://dx.doi.org/10.1136/gut.2005.081745] [PMID: 16547072] 
[56] 
Su, C.G.; Wen, X.; Bailey, S.T.; Jiang, W.; Rangwala, S.M.; Keilbaugh, S.A.; Flanigan, A.; Murthy, S.; Lazar, M.A.; Wu, G.D. A novel therapy for colitis utilizing PPAR-γ ligands to inhibit the epithelial inflammatory response. J. Clin. Invest.,  1999, 104(4), 383-389.
[http://dx.doi.org/10.1172/JCI7145] [PMID: 10449430] 
[57] 
Teresi, R.E.; Waite, K.A. PPARgamma, PTEN, and the Fight against Cancer. PPAR Res.,  2008, 2008, 932632.
[http://dx.doi.org/10.1155/2008/932632] [PMID: 19096712] 
[58] 
Patel, L.; Pass, I.; Coxon, P.; Downes, C.P.; Smith, S.A.; Macphee, C.H. Tumor suppressor and anti-inflammatory actions of PPARgamma agonists are mediated via upregulation of PTEN. Curr. Biol.,  2001, 11(10), 764-768.
[http://dx.doi.org/10.1016/S0960-9822(01)00225-1] [PMID: 11378386] 
[59] 
Chen, F.; Wang, M.; O’Connor, J.P.; He, M.; Tripathi, T.; Harrison, L.E. Phosphorylation of PPARgamma via active ERK1/2 leads to its physical association with p65 and inhibition of NF-kappabeta. J. Cell. Biochem.,  2003, 90(4), 732-744.
[http://dx.doi.org/10.1002/jcb.10668] [PMID: 14587029] 
[60] 
Wang, L.H.; Yang, X.Y.; Zhang, X.; Huang, J.; Hou, J.; Li, J.; Xiong, H.; Mihalic, K.; Zhu, H.; Xiao, W.; Farrar, W.L. Transcriptional inactivation of STAT3 by PPARgamma suppresses IL-6-responsive multiple myeloma cells. Immunity,  2004, 20(2), 205-218.
[http://dx.doi.org/10.1016/S1074-7613(04)00030-5] [PMID: 14975242] 
[61] 
Pascual, G.; Fong, A.L.; Ogawa, S.; Gamliel, A.; Li, A.C.; Perissi, V.; Rose, D.W.; Willson, T.M.; Rosenfeld, M.G.; Glass, C.K. A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-γ. Nature,  2005, 437(7059), 759-763.
[http://dx.doi.org/10.1038/nature03988] [PMID: 16127449] 
[62] 
Hou, Y.; Moreau, F.; Chadee, K. PPARγ is an E3 ligase that induces the degradation of NFκB/p65. Nat. Commun.,  2012, 3, 1300.
[http://dx.doi.org/10.1038/ncomms2270] [PMID: 23250430] 
[63] 
Lee, E.J.; Kim, S-J.; Hahn, Y-I.; Yoon, H-J.; Han, B.; Kim, K.; Lee, S.; Kim, K.P.; Suh, Y.G.; Na, H-K.; Surh, Y-J. 15-Keto prostaglandin E2 suppresses STAT3 signaling and inhibits breast cancer cell growth and progression. Redox Biol.,  2019, 23, 101175.
[http://dx.doi.org/10.1016/j.redox.2019.101175] [PMID: 31129031] 
[64] 
Lu, D.; Han, C.; Wu, T. 15-PGDH inhibits hepatocellular carcinoma growth through 15-keto-PGE2/PPARγ-mediated activation of p21WAF1/Cip1. Oncogene,  2014, 33(9), 1101-1112.
[http://dx.doi.org/10.1038/onc.2013.69] [PMID: 23542179] 
[65] 
Ratajczak, M.Z.; Zuba-Surma, E.; Kucia, M.; Reca, R.; Wojakowski, W.; Ratajczak, J. The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis, regeneration and tumorigenesis. Leukemia,  2006, 20(11), 1915-1924.
[http://dx.doi.org/10.1038/sj.leu.2404357] [PMID: 16900209] 
[66] 
Shi, Y.; Riese, D.J., II; Shen, J. The Role of the CXCL12/CXCR4/CXCR7 Chemokine Axis in Cancer. Front. Pharmacol.,  2020, 11, 574667.
[http://dx.doi.org/10.3389/fphar.2020.574667] [PMID: 33363463] 
[67] 
Rovito, D.; Gionfriddo, G.; Barone, I.; Giordano, C.; Grande, F.; De Amicis, F.; Lanzino, M.; Catalano, S.; Andò, S.; Bonofiglio, D. Ligand-activated PPARγ downregulates CXCR4 gene expression through a novel identified PPAR response element and inhibits breast cancer progression. Oncotarget,  2016, 7(40), 65109-65124.
[http://dx.doi.org/10.18632/oncotarget.11371] [PMID: 27556298] 
[68] 
Zhang, J.; Zhang, Y.; Xiao, F.; Liu, Y.; Wang, J.; Gao, H.; Rong, S.; Yao, Y.; Li, J.; Xu, G. The peroxisome proliferator-activated receptor γ agonist pioglitazone prevents NF-κB activation in cisplatin nephrotoxicity through the reduction of p65 acetylation via the AMPK-SIRT1/p300 pathway. Biochem. Pharmacol.,  2016, 101, 100-111.
[http://dx.doi.org/10.1016/j.bcp.2015.11.027] [PMID: 26673543] 
[69] 
Gutting, T.; Weber, C.A.; Weidner, P.; Herweck, F.; Henn, S.; Friedrich, T.; Yin, S.; Kzhyshkowska, J.; Gaiser, T.; Janssen, K-P.; Reindl, W.; Ebert, M.P.A.; Burgermeister, E. PPARγ-activation increases intestinal M1 macrophages and mitigates formation of serrated adenomas in mutant KRAS mice. OncoImmunology,  2018, 7(5), e1423168.
[http://dx.doi.org/10.1080/2162402X.2017.1423168] [PMID: 29721374] 
[70] 
Belvisi, M.G.; Mitchell, J.A. Targeting PPAR receptors in the airway for the treatment of inflammatory lung disease. Br. J. Pharmacol.,  2009, 158(4), 994-1003.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00373.x] [PMID: 19703165] 
[71] 
Mitchell, J.A.; Warner, T.D. Cyclo-oxygenase-2: pharmacology, physiology, biochemistry and relevance to NSAID therapy. Br. J. Pharmacol.,  1999, 128(6), 1121-1132.
[http://dx.doi.org/10.1038/sj.bjp.0702897] [PMID: 10578123] 
[72] 
Vane, J.R. Introduction: mechanism of action of NSAIDs. Br. J. Rheumatol.,  1996, 35(Suppl. 1), 1-3.
[http://dx.doi.org/10.1093/rheumatology/35.suppl_1.1] [PMID: 8630629] 
[73] 
Ulrich, C.M.; Bigler, J.; Potter, J.D. Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics. Nat. Rev. Cancer,  2006, 6(2), 130-140.
[http://dx.doi.org/10.1038/nrc1801] [PMID: 16491072] 
[74] 
Higuchi, T.; Takeuchi, A.; Munesue, S.; Yamamoto, N.; Hayashi, K.; Kimura, H.; Miwa, S.; Inatani, H.; Shimozaki, S.; Kato, T.; Aoki, Y.; Abe, K.; Taniguchi, Y.; Aiba, H.; Murakami, H.; Harashima, A.; Yamamoto, Y.; Tsuchiya, H. Anti-tumor effects of a nonsteroidal anti-inflammatory drug zaltoprofen on chondrosarcoma via activating peroxisome proliferator-activated receptor gamma and suppressing matrix metalloproteinase-2 expression. Cancer Med.,  2018, 7(5), 1944-1954.
[http://dx.doi.org/10.1002/cam4.1438] [PMID: 29573200] 
[75] 
Badawi, A.F.; Badr, M.Z. Chemoprevention of breast cancer by targeting cyclooxygenase-2 and peroxisome proliferator-activated receptor-gamma. (Review) Int. J. Oncol.,  2002, 20(6), 1109-1122.
[PMID: 12011987] 
[76] 
Han, S.; Inoue, H.; Flowers, L.C.; Sidell, N. Control of COX-2 gene expression through peroxisome proliferator-activated receptor gamma in human cervical cancer cells. Clin. Cancer Res.,  2003, 9(12), 4627-4635.
[PMID: 14555539] 
[77] 
Knopfová, L.; Šmarda, J. The use of Cox-2 and PPARγ signaling in anti-cancer therapies. Exp. Ther. Med.,  2010, 1(2), 257-264.
[http://dx.doi.org/10.3892/etm_00000040] [PMID: 22993537] 
[78] 
Eibl, G.; Takata, Y.; Boros, L.G.; Liu, J.; Okada, Y.; Reber, H.A.; Hines, O.J. Growth stimulation of COX-2-negative pancreatic cancer by a selective COX-2 inhibitor. Cancer Res.,  2005, 65(3), 982-990.
[PMID: 15705899] 
[79] 
Du, H.; Chen, X.; Zhang, J.; Chen, C. Inhibition of COX-2 expression by endocannabinoid 2-arachidonoylglycerol is mediated via PPAR-γ. Br. J. Pharmacol.,  2011, 163(7), 1533-1549.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01444.x] [PMID: 21501147] 
[80] 
Siddiqui, A.M.; Cui, X.; Wu, R.; Dong, W.; Zhou, M.; Hu, M.; Simms, H.H.; Wang, P. The anti-inflammatory effect of curcumin in an experimental model of sepsis is mediated by up-regulation of peroxisome proliferator-activated receptor-γ. Crit. Care Med.,  2006, 34(7), 1874-1882.
[http://dx.doi.org/10.1097/01.CCM.0000221921.71300.BF] [PMID: 16715036] 
[81] 
Ong, S.K.L.; Shanmugam, M.K.; Fan, L.; Fraser, S.E.; Arfuso, F.; Ahn, K.S.; Sethi, G.; Bishayee, A. Focus on Formononetin: Anticancer Potential and Molecular Targets. Cancers (Basel),  2019, 11(5), 11.
[http://dx.doi.org/10.3390/cancers11050611] [PMID: 31052435] 
[82] 
Choi, C-I. Astaxanthin as a Peroxisome Proliferator-Activated Receptor (PPAR) Modulator: Its Therapeutic Implications. Mar. Drugs,  2019, 17(4), 17.
[http://dx.doi.org/10.3390/md17040242] [PMID: 31018521] 
[83] 
Inoue, M.; Tanabe, H.; Matsumoto, A.; Takagi, M.; Umegaki, K.; Amagaya, S.; Takahashi, J. Astaxanthin functions differently as a selective peroxisome proliferator-activated receptor γ modulator in adipocytes and macrophages. Biochem. Pharmacol.,  2012, 84(5), 692-700.
[http://dx.doi.org/10.1016/j.bcp.2012.05.021] [PMID: 22732454] 
[84] 
Liu, S.; Su, M.; Song, S-J.; Hong, J.; Chung, H.Y.; Jung, J.H. An Anti-Inflammatory PPAR-γ Agonist from the Jellyfish-Derived Fungus Penicillium chrysogenum J08NF-4. J. Nat. Prod.,  2018, 81(2), 356-363.
[http://dx.doi.org/10.1021/acs.jnatprod.7b00846] [PMID: 29389121] 

Rights & Permissions Print Cite

Article Metrics

18

3

1

Journal Information

For Authors

For Editors

For Reviewers

Explore Articles

Open Access

Open Access Articles

For Visitors

DOI https://dx.doi.org/10.2174/1389557521666210422112740	Print ISSN 1389-5575
Publisher Name Bentham Science Publisher	Online ISSN 1875-5607

Mini-Reviews in Medicinal Chemistry

Peroxisome Proliferator-activated Receptor-γ As A Novel and Promising Target For Treating Cancer Via Regulation of Inflammation: A Brief Review

Abstract Play Pause

Graphical Abstract

Related Journals

Related Books

Related Articles

Abstract