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PPAR Research
Volume 2013 (2013), Article ID 109285, 11 pages
http://dx.doi.org/10.1155/2013/109285
Review Article

Therapeutic Implications of Targeting Energy Metabolism in Breast Cancer

1Graduate School of Life and Environmental Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba 305-8572, Japan
2Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia
3IRSHA, Bharati Vidyapeeth University, Pune 411043, India
4Omicsvista, Singapore 120417
5Rajiv Gandhi Institute of Information Technology and Biotechnology, Bharati Vidyapeeth University, Pune 411046, India

Received 24 October 2012; Accepted 23 December 2012

Academic Editor: Ruth Roberts

Copyright © 2013 Meena K. Sakharkar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. B. P. Kota, T. H. Huang, and B. D. Roufogalis, “An overview on biological mechanisms of PPARs,” Pharmacological Research, vol. 51, no. 2, pp. 85–94, 2005. View at Publisher · View at Google Scholar
  2. M. Tous, N. Ferré, A. Rull et al., “Dietary cholesterol and differential monocyte chemoattractant protein-1 gene expression in aorta and liver of apo E-deficient mice,” Biochemical and Biophysical Research Communications, vol. 340, no. 4, pp. 1078–1084, 2006. View at Publisher · View at Google Scholar · View at Scopus
  3. H. Castelein, T. Gulick, P. E. Declercq, G. P. Mannaerts, D. D. Moore, and M. I. Baes, “The peroxisome proliferator activated receptor regulates malic enzyme gene expression,” The Journal of Biological Chemistry, vol. 269, no. 43, pp. 26754–26758, 1994. View at Google Scholar · View at Scopus
  4. M. van Bilsen, G. J. van der Vusse, A. J. Gilde, M. Lindhout, and K. A. J. M. van der Lee, “Peroxisome proliferator-activated receptors: lipid binding proteins controling gene expression,” Molecular and Cellular Biochemistry, vol. 239, no. 1-2, pp. 131–138, 2002. View at Publisher · View at Google Scholar · View at Scopus
  5. J. J. Mansure, R. Nassim, and W. Kassouf, “Peroxisome proliferator-activated receptor gamma in bladder cancer: a promising therapeutic target in cancer,” in Cellular and Genetic Practices for Translational Medicine, vol. 8, no. 7, pp. 169–195, Research Signpost, 2011. View at Google Scholar
  6. J. I. Park, “The role of 15d-PGJ2, a natural ligand for peroxisome proliferator-activated receptor γ (PPARγ), in cancer,” Pharmacological Research, vol. 51, no. 2, pp. 85–94, 2005. View at Google Scholar
  7. C. C. Woo, S. Y. Loo, V. Gee et al., “Anticancer activity of thymoquinone in breast cancer cells: possible involvement of PPAR-γ pathway,” Biochemical Pharmacology, vol. 82, no. 5, pp. 464–475, 2011. View at Publisher · View at Google Scholar · View at Scopus
  8. Y. L. Lu, G. L. Li, H. L. Huang, J. Zhong, and L. C. Dai, “Peroxisome proliferator-activated receptor-γ 34C > G polymorphism and colorectal cancer risk: a meta-analysis,” World Journal of Gastroenterology, vol. 16, no. 17, pp. 2170–2175, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. G. Venkatachalam, A. P. Kumar, L. S. Yue, S. Pervaiz, M. V. Clement, and M. K. Sakharkar, “Computational identification and experimental validation of PPRE motifs in NHE1 and MnSOD genes of human,” BMC Genomics, vol. 10, supplement 3, article S5, 2009. View at Google Scholar · View at Scopus
  10. Y. Jeong, Y. Xie, W. Lee et al., “Research resource: diagnostic and therapeutic potential of nuclear receptor expression in lung cancer,” Molecular Endocrinology, vol. 26, no. 8, pp. 1443–1454, 2012. View at Publisher · View at Google Scholar
  11. W. Motomura, T. Okumura, N. Takahashi, T. Obara, and Y. Kohgo, “Activation of peroxisome proliferator-activated receptor γ by troglitazone inhibits cell growth through the increase of p27Kip1 in human pancreatic carcinoma cells,” Cancer Research, vol. 60, no. 19, pp. 5558–5564, 2000. View at Google Scholar · View at Scopus
  12. R. Govindarajan, L. Ratnasinghe, D. L. Simmons et al., “Thiazolidinediones and the risk of lung, prostate, and colon cancer in patients with diabetes,” Journal of Clinical Oncology, vol. 25, no. 12, pp. 1476–1481, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. H. N. Yu, Y. R. Lee, E. M. Noh et al., “Induction of G1 phase arrest and apoptosis in MDA-MB-231 breast cancer cells by troglitazone, a synthetic peroxisome proliferator-activated receptor γ (PPARγ) ligand,” Cell Biology International, vol. 32, no. 8, pp. 906–912, 2008. View at Publisher · View at Google Scholar · View at Scopus
  14. D. Bonofiglio, S. Aquila, S. Catalano et al., “Peroxisome proliferator-activated receptor-γ activates p53 gene promoter binding to the nuclear factor-κB sequence in human MCF7 breast cancer cells,” Molecular Endocrinology, vol. 20, no. 12, pp. 3083–3092, 2006. View at Publisher · View at Google Scholar · View at Scopus
  15. M. Pignatelli, C. Cocca, A. Santos, and A. Perez-Castillo, “Enhancement of BRCA1 gene expression by the peroxisome proliferator-activated receptor γ in the MCF-7 breast cancer cell line,” Oncogene, vol. 22, no. 35, pp. 5446–5450, 2003. View at Publisher · View at Google Scholar · View at Scopus
  16. G. L. Rubin, Y. Zhao, A. M. Kalus, and E. R. Simpson, “Peroxisome proliferator-activated receptor γ ligands inhibit estrogen biosynthesis in human breast adipose tissue: possible implications for breast cancer therapy,” Cancer Research, vol. 60, no. 6, pp. 1604–1608, 2000. View at Google Scholar · View at Scopus
  17. F. Turturro, E. Friday, R. Fowler, D. Surie, and T. Welbourne, “Troglitazone acts on cellular pH and DNA synthesis through a peroxisome proliferator-activated receptor γ-independent mechanism in breast cancer-derived cell lines,” Clinical Cancer Research, vol. 10, no. 20, pp. 7022–7030, 2004. View at Publisher · View at Google Scholar · View at Scopus
  18. A. G. Smith and G. E. Muscat, “Orphan nuclear receptors: therapeutic opportunities in skeletal muscle,” American Journal of Physiology, vol. 291, no. 2, pp. C203–C217, 2006. View at Publisher · View at Google Scholar
  19. S. Mukhopadhyay, S. K. Das, and S. Mukherjee, “Expression of Mn-superoxide dismutase gene in nontumorigenic and tumorigenic human mammary epithelial cells,” Journal of Biomedicine and Biotechnology, vol. 2004, no. 4, pp. 195–202, 2004. View at Publisher · View at Google Scholar · View at Scopus
  20. P. Fedele, N. Calvani, A. Marino et al., “Targeted agents to reverse resistance to endocrine therapy in metastatic breast cancer: where are we now and where are we going?” Critical Reviews in Oncology/Hematology, vol. 51, no. 2, pp. 85–94, 2012. View at Google Scholar
  21. T. N. Seyfried and L. M. Shelton, “Cancer as a metabolic disease,” Nutrition & Metabolism, vol. 7, article 7, 2010. View at Publisher · View at Google Scholar
  22. R. J. Klement and U. Kämmerer, “Is there a role for carbohydrate restriction in the treatment and prevention of cancer?” Nutrition & Metabolism, vol. 8, article 75, 2011. View at Publisher · View at Google Scholar
  23. X. Bi, Q. Lin, T. W. Foo, S. Joshi, T. You, H. M. Shen et al., “Proteomic analysis of colorectal cancer reveals alterations in metabolic pathways: mechanism of tumorigenesis,” Molecular & Cellular Proteomics, vol. 5, pp. 1119–1130, 2006. View at Publisher · View at Google Scholar
  24. R. D. Unwin, R. A. Craven, P. Harnden et al., “Proteomic changes in renal cancer and co-ordinate demonstration of both the glycolytic and mitochondrial aspects of the Warburg effect,” Proteomics, vol. 3, no. 8, pp. 1620–1632, 2003. View at Publisher · View at Google Scholar · View at Scopus
  25. B. Perroud, J. Lee, N. Valkova et al., “Pathway analysis of kidney cancer using proteomics and metabolic profiling,” Molecular Cancer, vol. 5, article 64, 2006. View at Publisher · View at Google Scholar · View at Scopus
  26. A. Isidoro, E. Casado, A. Redondo et al., “Breast carcinomas fulfill the Warburg hypothesis and provide metabolic markers of cancer prognosis,” Carcinogenesis, vol. 26, no. 12, pp. 2095–2104, 2005. View at Publisher · View at Google Scholar · View at Scopus
  27. L. M. Amon, S. J. Pitteri, C. I. Li et al., “Concordant release of glycolysis proteins into the plasma preceding a diagnosis of ER+ breast cancer,” Cancer Research, vol. 72, no. 8, pp. 1935–1942, 2012. View at Publisher · View at Google Scholar
  28. M. F. de Oliveira, N. D. Amoêdo, and F. D. Rumjanek, “Energy and redox homeostasis in tumor cells,” International Journal of Cell Biology, vol. 2012, Article ID 593838, 15 pages, 2012. View at Publisher · View at Google Scholar
  29. P. S. Ward and C. B. Thompson, “Metabolic reprogramming: a cancer hallmark even Warburg did not anticipate,” Cancer Cell, vol. 21, no. 3, pp. 297–308, 2012. View at Publisher · View at Google Scholar
  30. A. F. A. Mentis and E. Kararizou, “Metabolism and cancer: an up-to-date review of a mutual connection,” Asian Pacific Journal of Cancer Prevention, vol. 11, no. 6, pp. 1437–1444, 2010. View at Google Scholar · View at Scopus
  31. X. Zha, Q. Sun, and H. Zhang, “mTOR upregulation of glycolytic enzymes promotes tumor development,” Cell Cycle, vol. 10, no. 7, pp. 1015–1016, 2011. View at Publisher · View at Google Scholar · View at Scopus
  32. J. A. Menendez, L. Vellon, C. Oliveras-Ferraros, S. Cufí, and A. Vazquez-Martin, “mTOR-regulated senescence and autophagy during reprogramming of somatic cells to pluripotency: a roadmap from energy metabolism to stem cell renewal and aging,” Cell Cycle, vol. 10, no. 21, pp. 3658–3677, 2011. View at Publisher · View at Google Scholar
  33. A. C. Williams, T. J. Collard, and C. Paraskeva, “An acidic environment leads to p53 dependent induction of apoptosis in human adenoma and carcinoma cell lines: implications for clonal selection during colorectal carcinogenesis,” Oncogene, vol. 18, no. 21, pp. 3199–3204, 1999. View at Publisher · View at Google Scholar · View at Scopus
  34. S. Pavlides, D. Whitaker-Menezes, R. Castello-Cros et al., “The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma,” Cell Cycle, vol. 8, no. 23, pp. 3984–4001, 2009. View at Google Scholar · View at Scopus
  35. M. Guppy, P. Leedman, X. Zu, and V. Russell, “Contribution by different fuels and metabolic pathways to the total ATP turnover of proliferating MCF-7 breast cancer cells,” Biochemical Journal, vol. 364, part 1, pp. 309–315, 2002. View at Google Scholar · View at Scopus
  36. R. A. Gatenby, E. T. Gawlinski, A. F. Gmitro, B. Kaylor, and R. J. Gillies, “Acid-mediated tumor invasion: a multidisciplinary study,” Cancer Research, vol. 66, no. 10, pp. 5216–5223, 2006. View at Publisher · View at Google Scholar · View at Scopus
  37. P. I. Homem de Bittencourt Jr., C. M. Peres, M. M. Yano, M. H. Hirata, and R. Curi, “Pyruvate is a lipid precursor for rat lymphocytes in culture: evidence for a lipid exporting capacity,” Biochemistry and Molecular Biology International, vol. 30, no. 4, pp. 631–641, 1993. View at Google Scholar · View at Scopus
  38. H. Kondoh, M. E. Lleonart, D. Bernard, and J. Gil, “Protection from oxidative stress by enhanced glycolysis; a possible mechanism of cellular immortalization,” Histology and Histopathology, vol. 22, no. 1, pp. 85–90, 2007. View at Google Scholar · View at Scopus
  39. R. A. Gatenby and R. J. Gillies, “Why do cancers have high aerobic glycolysis?” Nature Reviews Cancer, vol. 4, no. 11, pp. 891–899, 2004. View at Publisher · View at Google Scholar · View at Scopus
  40. R. J. Gillies and R. A. Gatenby, “Adaptive landscapes and emergent phenotypes: why do cancers have high glycolysis?” Journal of Bioenergetics and Biomembranes, vol. 39, no. 3, pp. 251–257, 2007. View at Publisher · View at Google Scholar · View at Scopus
  41. G. Biamonti and J. F. Caceres, “Cellular stress and RNA splicing,” Trends in Biochemical Sciences, vol. 34, no. 3, pp. 146–153, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. A. E. Greijer, P. van der Groep, D. Kemming et al., “Up-regualtion of gene expression by hypoxia is mediated predominantly by hypoxia-inducible factor I (HIF-I),” Journal of Pathology, vol. 206, no. 3, pp. 291–304, 2005. View at Publisher · View at Google Scholar · View at Scopus
  43. N. Serkova and L. G. Boros, “Detection of resistance to imatinib by metabolic profiling: clinical and drug development implications,” American Journal of PharmacoGenomics, vol. 5, no. 5, pp. 293–302, 2005. View at Publisher · View at Google Scholar · View at Scopus
  44. P. Hsu and D. Sabatini, “Cancer cell metabolism: Warburg and beyond,” Cell, vol. 134, no. 5, pp. 703–707, 2008. View at Publisher · View at Google Scholar
  45. J. Dhahbi, H. Kim, P. Mote, R. Beaver, and S. Spindler, “Temporal linkage between the phenotypic and genomic responses to caloric restriction,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 15, pp. 5524–5529, 2004. View at Publisher · View at Google Scholar
  46. S. Y. Lunt and M. G. Vander Heiden, “Aerobic glycolysis: meeting the metabolic requirements of cell proliferation,” Annual Review of Cell and Developmental Biology, vol. 27, pp. 441–464, 2011. View at Publisher · View at Google Scholar
  47. S. John, J. N. Weiss, and B. Ribalet, “Subcellular localization of hexokinases I and II directs the metabolic fate of glucose,” PLoS ONE, vol. 6, no. 3, Article ID e17674, 2011. View at Publisher · View at Google Scholar · View at Scopus
  48. S. P. Mathupala, Y. H. Ko, and P. L. Pedersen, “Hexokinase-2 bound to mitochondria: cancer's stygian link to the “Warburg effect” and a pivotal target for effective therapy,” Seminars in Cancer Biology, vol. 19, no. 1, pp. 17–24, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. S. P. Mathupala, Y. H. Ko, and P. L. Pedersen, “Hexokinase II: cancer's double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria,” Oncogene, vol. 25, no. 34, pp. 4777–4786, 2006. View at Publisher · View at Google Scholar · View at Scopus
  50. E. E. Mendoza, M. G. Pocceschi, X. Kong et al., “Control of glycolytic flux by AMP-activated protein kinase in tumor cells adapted to low pH,” Translational Oncology, vol. 5, no. 3, pp. 208–216, 2012. View at Google Scholar
  51. E. C. Ferguson and J. C. Rathmell, “New roles for pyruvate kinase M2: working out the Warburg effect,” Trends in Biochemical Sciences, vol. 33, no. 8, pp. 359–362, 2008. View at Publisher · View at Google Scholar · View at Scopus
  52. C. J. David, M. Chen, M. Assanah, P. Canoll, and J. L. Manley, “HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer,” Nature, vol. 463, no. 7279, pp. 364–368, 2010. View at Publisher · View at Google Scholar · View at Scopus
  53. B. Shashni, K. R. Sakharkar, Y. Nagasaki, and M. K. Sakharkar, “Glycolytic enzymes PGK1 and PKM2 as novel transcriptional targets of PPAR gamma in breast cancer pathophysiology,” Journal of Drug Targeting. In press.
  54. G. Venkatachalam, A. P. Kumar, K. R. Sakharkar, S. Thangavel, M. V. Clement, and M. K. Sakharkar, “PPARγ disease gene network and identification of therapeutic targets for prostate cancer,” Journal of Drug Targeting, vol. 19, no. 9, pp. 781–796, 2011. View at Publisher · View at Google Scholar
  55. A. Lagana, J. Vadnais, P. U. Le et al., “Regulation of the formation of tumor cell pseudopodia by the Na(+)/H(+) exchanger NHE1,” Journal of Cell Science, vol. 113, part 20, pp. 3649–3662, 2000. View at Google Scholar · View at Scopus
  56. L. K. Putney, S. P. Denker, and D. L. Barber, “The changing face of the Na+/H+ exchanger, NHE1: structure, regulation, and cellular actions,” Annual Review of Pharmacology and Toxicology, vol. 42, pp. 527–552, 2002. View at Publisher · View at Google Scholar · View at Scopus
  57. S. J. Reshkin, A. Bellizzi, S. Caldeira et al., “Na+/H+ exchanger-dependent intracellular alkalinization is an early event in malignant transformation and plays an essential role in the development of subsequent transformation-associated phenotypes,” The FASEB Journal, vol. 14, no. 14, pp. 2185–2197, 2000. View at Google Scholar · View at Scopus
  58. S. Grinstein and S. J. Dixon, “Ion transport, membrane potential, and cytoplasmic pH in lymphocytes: changes during activation,” Physiological Reviews, vol. 69, no. 2, pp. 417–481, 1989. View at Google Scholar · View at Scopus
  59. S. M. Bell, S. M. Schreiner, P. J. Schultheis et al., “Targeted disruption of the murine NHE1 locus induces ataxia, growth retardation, and seizures,” American Journal of Physiology, vol. 276, pp. C788–C795, 1999. View at Google Scholar
  60. J. Pouyssegur, A. Franchi, and G. Pages, “pHi, aerobic glycolysis and vascular endothelial growth factor in tumour growth,” Novartis Foundation Symposium, vol. 240, pp. 186–196, 2001. View at Google Scholar
  61. F. Turturro, E. Friday, R. Fowler, D. Surie, and T. Welbourne, “Troglitazone acts on cellular pH and DNA synthesis through a peroxisome proliferator-activated receptor γ-independent mechanism in breast cancer-derived cell lines,” Clinical Cancer Research, vol. 10, no. 20, pp. 7022–7030, 2004. View at Publisher · View at Google Scholar · View at Scopus
  62. S. Akram, H. F. C. Teong, L. Fliegel, S. Pervaiz, and M. V. Clément, “Reactive oxygen species-mediated regulation of the Na+-H+ exchanger 1 gene expression connects intracellular redox status with cells' sensitivity to death triggers,” Cell Death and Differentiation, vol. 13, no. 4, pp. 628–641, 2006. View at Publisher · View at Google Scholar · View at Scopus
  63. S. A. Kliewer, J. M. Lenhard, T. M. Willson, I. Patel, D. C. Morris, and J. M. Lehmann, “A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor γ and promotes adipocyte differentiation,” Cell, vol. 83, no. 5, pp. 813–819, 1995. View at Google Scholar · View at Scopus
  64. H. Pelicano, D. Carney, and P. Huang, “ROS stress in cancer cells and therapeutic implications,” Drug Resistance Updates, vol. 7, no. 2, pp. 97–110, 2004. View at Publisher · View at Google Scholar · View at Scopus
  65. L. Gibellini, M. Pinti, M. Nasi et al., “Interfering with ROS metabolism in cancer cells: the potential role of quercetin,” Cancers, vol. 2, no. 2, pp. 1288–1311, 2010. View at Publisher · View at Google Scholar · View at Scopus
  66. K. B. Storey, “Oxidative stress: animal adaptations in nature,” Brazilian Journal of Medical and Biological Research, vol. 29, no. 12, pp. 1715–1733, 1996. View at Google Scholar
  67. A. M. L. Janssen, C. B. Bosman, W. van Duijn et al., “Superoxide dismutases in gastric and esophageal cancer and the prognostic impact in gastric cancer,” Clinical Cancer Research, vol. 6, no. 8, pp. 3183–3192, 2000. View at Google Scholar · View at Scopus
  68. O. Kanbagli, G. Ozdemirler, T. Bulut, S. Yamaner, G. Aykaç-Toker, and M. Uysal, “Mitochondrial lipid peroxides and antioxidant enzymes in colorectal adenocarcinoma tissues,” Japanese Journal of Cancer Research, vol. 91, no. 12, pp. 1258–1263, 2000. View at Google Scholar
  69. K. Punnonen, M. Ahotupa, K. Asaishi, M. Hyöty, R. Kudo, and R. Punnonen, “Antioxidant enzyme activities and oxidative stress in human breast cancer,” Journal of Cancer Research and Clinical Oncology, vol. 120, no. 6, pp. 374–377, 1994. View at Google Scholar · View at Scopus
  70. C. S. Cobbs, D. S. Levi, K. Aldape, and M. A. Israel, “Manganese superoxide dismutase expression in human central nervous system tumors,” Cancer Research, vol. 56, no. 14, pp. 3192–3195, 1996. View at Google Scholar · View at Scopus
  71. E. A. Hileman, G. Achanta, and P. Huang, “Superoxide dismutase: an emerging target for cancer therapeutics,” Expert Opinion on Therapeutic Targets, vol. 5, no. 6, pp. 697–710, 2001. View at Google Scholar · View at Scopus
  72. T. Nishiura, K. Suzuki, T. Kawaguchi et al., “Elevated serum manganese superoxide dismutase in acute leukemias,” Cancer Letters, vol. 62, no. 3, pp. 211–215, 1992. View at Publisher · View at Google Scholar · View at Scopus
  73. S. Senthil, R. M. Veerappan, M. Ramakrishna Rao, and K. V. Pugalendi, “Oxidative stress and antioxidants in patients with cardiogenic shock complicating acute myocardial infarction,” Clinica Chimica Acta, vol. 348, no. 1-2, pp. 131–137, 2004. View at Publisher · View at Google Scholar · View at Scopus
  74. S. P. Weisberg, D. McCann, M. Desai, M. Rosenbaum, R. L. Leibel, and A. W. Ferrante Jr., “Obesity is associated with macrophage accumulation in adipose tissue,” The Journal of Clinical Investigation, vol. 112, no. 12, pp. 1796–1808, 2003. View at Publisher · View at Google Scholar · View at Scopus
  75. G. R. Hajer, T. W. van Haeften, and F. L. Visseren, “Adipose tissue dysfunction in obesity, diabetes, and vascular diseases,” European Heart Journal, vol. 29, no. 24, pp. 2959–2971, 2008. View at Publisher · View at Google Scholar
  76. C. Kumar-Sinha, K. W. Ignatoski, M. E. Lippman, S. P. Ethier, and A. M. Chinnaiyan, “Transcriptome analysis of HER2 reveals a molecular connection to fatty acid synthesis,” Cancer Research, vol. 63, no. 1, pp. 132–139, 2003. View at Google Scholar · View at Scopus
  77. J. A. Menendez, I. Mehmi, V. A. Verma, P. K. Teng, and R. Lupu, “Pharmacological inhibition of fatty acid synthase (FAS): a novel therapeutic approach for breast cancer chemoprevention through its ability to suppress Her-2/neu (erbB-2) oncogene-induced malignant transformation,” Molecular Carcinogenesis, vol. 41, no. 3, pp. 164–178, 2004. View at Publisher · View at Google Scholar · View at Scopus
  78. J. A. Menendez, B. P. Oza, E. Atlas, V. A. Verma, I. Mehmi, and R. Lupu, “Inhibition of tumor-associated fatty acid synthase activity antagonizes estradiol- and tamoxifen-induced agonist transactivation of estrogen receptor (ER) in human endometrial adenocarcinoma cells,” Oncogene, vol. 23, no. 28, pp. 4945–4958, 2004. View at Publisher · View at Google Scholar · View at Scopus
  79. S. Hardy, Y. Langelier, and M. Prentki, “Oleate activates phosphatidylinositol 3-kinase and promotes proliferation and reduces apoptosis of MDA-MB-231 breast cancer cells, whereas palmitate has opposite effects,” Cancer Research, vol. 60, no. 22, pp. 6353–6358, 2000. View at Google Scholar · View at Scopus
  80. S. Hardy, W. El-Assaad, E. Przybytkowski, E. Joly, M. Prentki, and Y. Langelier, “Saturated fatty acid-induced apoptosis in MDA-MB-231 breast cancer cells. A role for cardiolipin,” The Journal of Biological Chemistry, vol. 278, no. 34, pp. 31861–31870, 2003. View at Publisher · View at Google Scholar · View at Scopus
  81. B. Desvergne and W. Wahli, “Peroxisome proliferators-activated receptors: nuclear control of metabolism,” Endocrine Reviews, vol. 20, pp. 649–688, 1999. View at Publisher · View at Google Scholar
  82. G. Medina-Gomez, S. Gray, and A. Vidal-Puig, “Adipogenesis and lipotoxicity: role of peroxisome proliferator-activated receptor γ (PPARγ) and PPARγcoactivator-1 (PGC1),” Public Health Nutrition, vol. 10, no. 10, pp. 1132–1137, 2007. View at Publisher · View at Google Scholar · View at Scopus
  83. L. Han, R. Zhou, J. Niu, M. A. McNutt, P. Wang, and T. Tong, “SIRT1 is regulated by a PPARγ-SIRT1 negative feedback loop associated with senescence,” Nucleic Acids Research, vol. 38, no. 21, pp. 7458–7471, 2010. View at Google Scholar
  84. E. Giovannucci, D. M. Harlan, M. C. Archer et al., “Diabetes and cancer: a consensus report,” CA Cancer Journal for Clinicians, vol. 60, no. 4, pp. 207–221, 2010. View at Publisher · View at Google Scholar · View at Scopus
  85. S. Liao, J. Li, L. Wang, Y. Zhang, and C. Wang, “Type 2 diabetes mellitus and characteristics of breast cancer in China,” The Asian Pacific Journal of Cancer Prevention, vol. 11, pp. 933–937, 2010. View at Google Scholar
  86. P. Boyle, M. Boniol, A. Koechlin et al., “Diabetes and breast cancer risk: a meta-analysis,” British Journal of Cancer, vol. 51, no. 2, pp. 85–94, 2012. View at Publisher · View at Google Scholar
  87. D. O. Carpenter, “Environmental contaminants as risk factors for developing diabetes,” Reviews on Environmental Health, vol. 23, no. 1, pp. 59–74, 2008. View at Google Scholar
  88. J. T. Huang, J. S. Welch, M. Ricote et al., “Interleukin-4-dependent production of PPAR-γ ligands in macrophages by 12/15-lipoxygenase,” Nature, vol. 400, no. 6742, pp. 378–382, 1999. View at Publisher · View at Google Scholar · View at Scopus
  89. L. Nagy, P. Tontonoz, J. G. A. Alvarez, H. Chen, and R. M. Evans, “Oxidized LDL regulates macrophage gene expression through ligand activation of PPARγ,” Cell, vol. 93, no. 2, pp. 229–240, 1998. View at Publisher · View at Google Scholar · View at Scopus
  90. J. Berger, P. Bailey, C. Biswas et al., “Thiazolidinediones produce a conformational change in peroxisomal proliferator-activated receptor-γ: binding and activation correlate with antidiabetic actions in db/db mice,” Endocrinology, vol. 137, no. 10, pp. 4189–4195, 1996. View at Publisher · View at Google Scholar · View at Scopus
  91. J. M. Lehmann, L. B. Moore, T. A. Smith-Oliver, W. O. Wilkison, T. M. Willson, and S. A. Kliewer, “An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ),” The Journal of Biological Chemistry, vol. 270, no. 22, pp. 12953–12956, 1995. View at Publisher · View at Google Scholar · View at Scopus
  92. K. G. Lambe and J. D. Tugwood, “A human peroxisome-proliferator-activated receptor-γ is activated by inducers of adipogenesis, including thiazalidinedione drugs,” European Journal of Biochemistry, vol. 239, no. 1, pp. 1–7, 1996. View at Google Scholar · View at Scopus
  93. J. J. Acton III, R. M. Black, A. B. Jones et al., “Benzoyl 2-methyl indoles as selective PPARgamma modulators,” Bioorganic & Medicinal Chemistry Letters, vol. 15, pp. 357–362, 2005. View at Google Scholar
  94. A. M. Fair, Q. Dai, X. O. Shu et al., “Energy balance, insulin resistance biomarkers, and breast cancer risk,” Cancer Detection and Prevention, vol. 31, no. 3, pp. 214–219, 2007. View at Publisher · View at Google Scholar · View at Scopus
  95. P. Pisani, “Hyper-insulinaemia and cancer, meta-analyses of epidemiological studies,” Archives of Physiology and Biochemistry, vol. 114, no. 1, pp. 63–70, 2008. View at Publisher · View at Google Scholar · View at Scopus
  96. A. Belfiore, M. Genua, and R. Malaguarnera, “PPAR-γ agonists and their effects on IGF-I receptor signaling: implications for cancer,” PPAR Research, vol. 2009, Article ID 830501, 18 pages, 2009. View at Publisher · View at Google Scholar · View at Scopus
  97. H. Y. Järvinen, “Thiazolidinediones,” The New England Journal of Medicine, vol. 351, no. 11, pp. 1106–1118, 2004. View at Publisher · View at Google Scholar
  98. H. J. Burstein, G. D. Demetri, E. Mueller, P. Sarraf, B. M. Spiegelman, and E. P. Winer, “Use of the peroxisome proliferator-activated receptor (PPAR) γ ligand troglitazone as treatment for refractory breast cancer: a phase II study,” Breast Cancer Research and Treatment, vol. 79, no. 3, pp. 391–397, 2003. View at Publisher · View at Google Scholar · View at Scopus
  99. S. Kawa, T. Nikaido, H. Unno, N. Usuda, K. Nakayama, and K. Kiyosawa, “Growth inhibition and differentiation of pancreatic cancer cell lines by PPARγ ligand troglitazone,” Pancreas, vol. 24, no. 1, pp. 1–7, 2002. View at Publisher · View at Google Scholar · View at Scopus
  100. E. Mueller, M. Smith, P. Sarraf et al., “Effects of ligand activation of peroxisome proliferator-activated receptor γ in human prostate cancer,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 20, pp. 10990–10995, 2000. View at Publisher · View at Google Scholar
  101. T. Shimada, K. Kojima, K. Yoshiura, H. Hiraishi, and A. Terano, “Characteristics of the peroxisome proliferator activated receptor γ (PPARγ) ligand induced apoptosis in colon cancer cells,” Gut, vol. 50, no. 5, pp. 658–664, 2002. View at Publisher · View at Google Scholar · View at Scopus
  102. M. Ricote, A. C. Li, T. M. Willson, C. J. Kelly, and C. K. Glass, “The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation,” Nature, vol. 391, no. 6662, pp. 79–82, 1998. View at Publisher · View at Google Scholar · View at Scopus
  103. U. Kintscher, C. J. Lyon, and R. E. Law, “Angiotensin II, PPAR-gamma and atherosclerosis,” Frontiers in Bioscience, vol. 1, pp. 359–369, 2004. View at Google Scholar
  104. G. Helbig, K. W. Christopherson, P. Bhat-Nakshatri et al., “NF-κB promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4,” The Journal of Biological Chemistry, vol. 278, no. 24, pp. 21631–21638, 2003. View at Publisher · View at Google Scholar · View at Scopus
  105. B. Sung, S. Park, B. P. Yu, and H. Y. Chung, “Amelioration of age-related inflammation and oxidative stress by PPARγ activator: suppression of NF-κB by 2, 4-thiazolidinedione,” Experimental Gerontology, vol. 41, pp. 590–599, 2006. View at Publisher · View at Google Scholar
  106. B. Sung, S. Park, B. P. Yu, and H. Y. Chung, “Modulation of PPAR in aging, inflammation, and calorie restriction,” The Journals of Gerontology A, vol. 59, no. 10, pp. B997–B1006, 2004. View at Publisher · View at Google Scholar
  107. K. L. Houseknecht, B. M. Cole, and P. J. Steele, “Peroxisome proliferator-activated receptor gamma (PPARγ) and its ligands: a review,” Domestic Animal Endocrinology, vol. 22, no. 1, pp. 1–23, 2002. View at Publisher · View at Google Scholar · View at Scopus
  108. M. Ricote, A. C. Li, T. M. Willson, J. Kelly, and C. K. Glass, “The peroxisome proliferators activated receptor-gamma is a negative regulator of macrophage activation,” Nature, vol. 391, pp. 79–82, 1998. View at Publisher · View at Google Scholar
  109. T. K. Kerppola, D. Luk, and T. Curran, “Fos is a preferential target of glucocorticoid receptor inhibition of AP-1 activity in vitro,” Molecular and Cellular Biology, vol. 13, pp. 3782–3791, 1993. View at Google Scholar
  110. Y. Kamei, L. Xu, T. Heinzel et al., “A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors,” Cell, vol. 85, no. 3, pp. 403–414, 1996. View at Publisher · View at Google Scholar · View at Scopus
  111. C. K. Glass and M. G. Rosenfeld, “The coregulator exchange in transcriptional functions of nuclear receptors,” Genes & Development, vol. 14, pp. 121–141, 2000. View at Google Scholar
  112. S. Tyagi, P. Gupta, A. S. Saini, C. Kaushal, and S. Sharma, “The peroxisome proliferator-activated receptor: a family of nuclear receptors role in various diseases,” Journal of Advanced Pharmaceutical Technology & Research, vol. 2, no. 4, pp. 236–240, 2011. View at Publisher · View at Google Scholar