Table of Contents Author Guidelines Submit a Manuscript
PPAR Research
Volume 2008, Article ID 254108, 8 pages
http://dx.doi.org/10.1155/2008/254108
Review Article

Activated PPAR Targets Surface and Intracellular Signals That Inhibit the Proliferation of Lung Carcinoma Cells

1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University School of Medicine, 615 Michael Street Suite 205, Atlanta, GA 30322, USA
2Atlanta VA Medical Center, Department of Medicine, 1670 Clairmont Road, Decatur, GA 30033, USA

Received 28 April 2008; Accepted 24 June 2008

Academic Editor: Dipak Panigrahy

Copyright © 2008 Shou Wei Han and Jesse Roman. 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. D. Gilligan, M. Nicolson, I. Smith et al., “Preoperative chemotherapy in patients with resectable non-small cell lung cancer: results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review,” The Lancet, vol. 369, no. 9577, pp. 1929–1937, 2007. View at Publisher · View at Google Scholar
  2. D. S. Ettinger, “Overview and state of the art in the management of lung cancer,” Oncology, vol. 18, no. 7, supplement 4, pp. 3–9, 2004. View at Google Scholar
  3. M. Pirozynski, “100 years of lung cancer,” Respiratory Medicine, vol. 100, no. 12, pp. 2073–2084, 2006. View at Publisher · View at Google Scholar
  4. J. Roman, “Peroxisome proliferator-activated receptor gamma and lung cancer biology: implications for therapy,” Journal of Investigative Medicine, vol. 56, no. 2, pp. 528–533, 2008. View at Google Scholar
  5. A. Krishnan, S. A. Nair, and M. R. Pillai, “Biology of PPARγ in cancer: a critical review on existing lacunae,” Current Molecular Medicine, vol. 7, no. 6, pp. 532–540, 2007. View at Publisher · View at Google Scholar
  6. S. Han, J. D. Ritzenthaler, B. Wingerd, and J. Roman, “Activation of peroxisome proliferator-activated receptor β/δ (PPARβ/δ) increases the expression of prostaglandin E2 receptor subtype EP4: the roles of phosphatidylinositol 3-kinase and CCAAT/enhancer-binding protein β,” Journal of Biological Chemistry, vol. 280, no. 39, pp. 33240–33249, 2005. View at Publisher · View at Google Scholar
  7. L. Fajas, D. Auboeuf, E. Raspé et al., “The organization, promoter analysis, and expression of the human PPAR? gene,” Journal of Biological Chemistry, vol. 272, no. 30, pp. 18779–18789, 1997. View at Publisher · View at Google Scholar
  8. L. Fajas, J.-C. Fruchart, and J. Auwerx, “PPARγ3 mRNA: a distinct PPARγ mRNA subtype transcribed from an independent promoter,” FEBS Letters, vol. 438, no. 1-2, pp. 55–60, 1998. View at Publisher · View at Google Scholar
  9. B. M. Spiegelman, “PPARγ in monocytes: less pain, any gain?” Cell, vol. 93, no. 2, pp. 153–155, 1998. View at Publisher · View at Google Scholar
  10. P. Tontonoz, E. Hu, and B. M. Spiegelman, “Regulation of adipocyte gene expression and differentiation by peroxisome proliferator activated receptor γ,” Current Opinion in Genetics & Development, vol. 5, no. 5, pp. 571–576, 1995. View at Publisher · View at Google Scholar
  11. M. Lehrke and M. A. Lazar, “The many faces of PPARγ,” Cell, vol. 123, no. 6, pp. 993–999, 2005. View at Publisher · View at Google Scholar
  12. R. K. Semple, V. K. K. Chatterjee, and S. O'Rahilly, “PPARγ and human metabolic disease,” The Journal of Clinical Investigation, vol. 116, no. 3, pp. 581–589, 2006. View at Publisher · View at Google Scholar
  13. E. Elstner, C. Müller, K. Koshizuka et al., “Ligands for peroxisome proliferator-activated receptor? and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 15, pp. 8806–8811, 1998. View at Publisher · View at Google Scholar
  14. G. Y. Zhang, N. Ahmed, C. Riley et al., “Enhanced expression of peroxisome proliferator-activated receptor gamma in epithelial ovarian carcinoma,” British Journal of Cancer, vol. 92, no. 1, pp. 113–119, 2005. View at Publisher · View at Google Scholar
  15. V. G. Keshamouni, R. C. Reddy, D. A. Arenberg et al., “Peroxisome proliferator-activated receptor-? activation inhibits tumor progression in non-small-cell lung cancer,” Oncogene, vol. 23, no. 1, pp. 100–108, 2004. View at Publisher · View at Google Scholar
  16. D. Panigrahy, S. Singer, L. Q. Shen et al., “PPAR? ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis,” The Journal of Clinical Investigation, vol. 110, no. 7, pp. 923–932, 2002. View at Publisher · View at Google Scholar
  17. R. A. Daynes and D. C. Jones, “Emerging roles of PPARs in inflammation and immunity,” Nature Reviews Immunology, vol. 2, no. 10, pp. 748–759, 2002. View at Publisher · View at Google Scholar
  18. C. Jiang, A. T. Ting, and B. Seed, “PPAR-γ agonists inhibit production of monocyte inflammatory cytokines,” Nature, vol. 391, no. 6662, pp. 82–86, 1998. View at Publisher · View at Google Scholar
  19. M. Ricote, J. Huang, L. Fajas et al., “Expression of the peroxisome proliferator-activated receptor ? (PPAR?) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 13, pp. 7614–7619, 1998. View at Publisher · View at Google Scholar
  20. 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),” Journal of Biological Chemistry, vol. 270, no. 22, pp. 12953–12956, 1995. View at Publisher · View at Google Scholar
  21. P. B. Watkins and R. W. Whitcomb, “Hepatic dysfunction associated with troglitazone,” The New England Journal of Medicine, vol. 338, no. 13, pp. 916–917, 1998. View at Publisher · View at Google Scholar
  22. T. Shibata, K. Matsui, K. Nagao, H. Shinkai, F. Yonemori, and K. Wakitani, “Pharmacological profiles of a novel oral antidiabetic agent, JTT-501, an isoxazolidinedione derivative,” European Journal of Pharmacology, vol. 364, no. 2-3, pp. 211–219, 1999. View at Publisher · View at Google Scholar
  23. N. Suh, Y. Wang, C. R. Williams et al., “A new ligand for the peroxisome proliferator-activated receptor-? (PPAR-?), GW7845, inhibits rat mammary carcinogenesis,” Cancer Research, vol. 59, no. 22, pp. 5671–5673, 1999. View at Google Scholar
  24. G. Chêne, M. Dubourdeau, P. Balard et al., “n-3 and n-6 Polyunsaturated fatty acids induce the expression of COX-2 via PPAR? activation in human keratinocyte HaCaT cells,” Biochimica et Biophysica Acta, vol. 1771, no. 5, pp. 576–589, 2007. View at Publisher · View at Google Scholar
  25. 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
  26. F. J. Schopfer, Y. Lin, P. R. S. Baker et al., “Nitrolinoleic acid: an endogenous peroxisome proliferator-activated receptor ? ligand,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 7, pp. 2340–2345, 2005. View at Publisher · View at Google Scholar
  27. B. Y. Hwang, J.-H. Lee, J. B. Nam, H. S. Kim, Y. S. Hong, and J. J. Lee, “Two new furanoditerpenes from Saururus chinenesis and their effects on the activation of peroxisome proliferator-activated receptor γ,” Journal of Natural Products, vol. 65, no. 4, pp. 616–617, 2002. View at Publisher · View at Google Scholar
  28. Y.-C. Liang, S.-H. Tsai, D.-C. Tsai, S.-Y. Lin-Shiau, and J.-K. Lin, “Suppression of inducible cyclooxygenase and nitric oxide synthase through activation of peroxisome proliferator-activated receptor-γ by flavonoids in mouse macrophages,” FEBS Letters, vol. 496, no. 1, pp. 12–18, 2001. View at Publisher · View at Google Scholar
  29. M. Kuroda, Y. Mimaki, Y. Sashida et al., “Phenolics with PPAR-? ligand-Binding activity obtained from licorice (Glycyrrhiza uralensis Roots) and ameliorative effects of glycyrin on genetically diabetic KK-Ay mice,” Bioorganic & Medicinal Chemistry Letters, vol. 13, no. 24, pp. 4267–4272, 2003. View at Publisher · View at Google Scholar
  30. J. Xu, Y. Fu, and A. Chen, “Activation of peroxisome proliferator-activated receptor-γ contributes to the inhibitory effects of curcumin on rat hepatic stellate cell growth,” American Journal of Physiology, vol. 285, no. 1, pp. G20–G30, 2003. View at Google Scholar
  31. S. Zheng and A. Chen, “Activation of PPARγ is required for curcumin to induce apoptosis and to inhibit the expression of extracellular matrix genes in hepatic stellate cells in vitro,” Biochemical Journal, vol. 384, no. 1, pp. 149–157, 2004. View at Publisher · View at Google Scholar
  32. M. J. Reginato, S. T. Bailey, S. L. Krakow et al., “A potent antidiabetic thiazolidinedione with unique peroxisome proliferator-activated receptor ?-activating properties,” Journal of Biological Chemistry, vol. 273, no. 49, pp. 32679–32684, 1998. View at Publisher · View at Google Scholar
  33. K. Inoue, Y. Kawahito, Y. Tsubouchi et al., “Expression of peroxisome proliferator-activated receptor (PPAR)-? in human lung cancer,” Anticancer Research, vol. 21, no. 4A, pp. 2471–2476, 2001. View at Google Scholar
  34. S. V. Fulzele, A. Chatterjee, M. S. Shaik, T. Jackson, N. Ichite, and M. Singh, “15-deoxy-Δ12,14-prostaglandin J2 enhances docetaxel anti-tumor activity against A549 and H460 non-small-cell lung cancer cell lines and xenograft tumors,” Anti-Cancer Drugs, vol. 18, no. 1, pp. 65–78, 2007. View at Publisher · View at Google Scholar
  35. K. Y. Kim, J. H. Ahn, and H. G. Cheon, “Apoptotic action of PPARγ activation in human non-small cell lung cancer is mediated via proline oxidase-induced ROS formation,” Molecular Pharmacology, vol. 72, no. 3, pp. 674–685, 2007. View at Publisher · View at Google Scholar
  36. T. Satoh, M. Toyoda, H. Hoshino et al., “Activation of peroxisome proliferator-activated receptor-? stimulates the growth arrest and DNA-damage inducible 153 gene in non-small cell lung carcinoma cells,” Oncogene, vol. 21, no. 14, pp. 2171–2180, 2002. View at Publisher · View at Google Scholar
  37. M. Li, T. W. Lee, A. P. C. Yim, T. S. K. Mok, and G. G. Chen, “Apoptosis induced by troglitazone is both peroxisome proliferator-activated receptor-γ- and ERK-dependent in human non-small lung cancer cells,” Journal of Cellular Physiology, vol. 209, no. 2, pp. 428–438, 2006. View at Publisher · View at Google Scholar
  38. M. Li, T. W. Lee, T. S. K. Mok, T. D. Warner, A. P. C. Yim, and G. G. Chen, “Activation of peroxisome proliferator-activated receptor-γ by troglitazone (TGZ) inhibits human lung cell growth,” Journal of Cellular Biochemistry, vol. 96, no. 4, pp. 760–774, 2005. View at Publisher · View at Google Scholar
  39. W. Zou, X. Liu, P. Yue, F. R. Khuri, and S. Y. Sun, “PPARγ ligands enhance TRAIL-induced apoptosis through DR5 upregulation and c-FLIP downregulation in human lung cancer cells,” Cancer Biology and Therapy, vol. 6, no. 1, pp. 99–106, 2007. View at Google Scholar
  40. S. Han, N. Sidell, P. B. Fisher, and J. Roman, “Up-regulation of p21 gene expression by peroxisome proliferator-activated receptor γ in human lung carcinoma cells,” Clinical Cancer Research, vol. 10, no. 6, pp. 1911–1919, 2004. View at Publisher · View at Google Scholar
  41. W. Zhang, H. Zhang, and L. Xing, “Influence of ciglitazone on A549 cells growth in vitro and in vivo and mechanism,” Journal of Huazhong University of Science and Technology. Medical Sciences, vol. 26, no. 1, pp. 36–39, 2006. View at Google Scholar
  42. S. Han and J. Roman, “Rosiglitazone suppresses human lung carcinoma cell growth through PPARγ-dependent and PPARγ-independent signal pathways,” Molecular Cancer Therapeutics, vol. 5, no. 2, pp. 430–437, 2006. View at Publisher · View at Google Scholar
  43. S. Han, Y. Zheng, and J. Roman, “Rosiglitazone, an agonist of PPARγ, inhibits non-small cell carcinoma cell proliferation in part through activation of tumor sclerosis complex-2,” PPAR Research, vol. 2007, Article ID 29632, 8 pages, 2007. View at Publisher · View at Google Scholar
  44. S. Y. Lee, G. Y. Hur, K. H. Jung et al., “PPAR-? agonist increase gefitinib's antitumor activity through PTEN expression,” Lung Cancer, vol. 51, no. 3, pp. 297–301, 2006. View at Publisher · View at Google Scholar
  45. G. Hannigan, A. A. Troussard, and S. Dedhar, “Integrin-linked kinase: a cancer therapeutic target unique among its ILK,” Nature Reviews Cancer, vol. 5, no. 1, pp. 51–63, 2005. View at Publisher · View at Google Scholar
  46. S. Han and J. Roman, “Suppression of prostaglandin E2 receptor subtype EP2 by PPARγ ligands inhibits human lung carcinoma cell growth,” Biochemical and Biophysical Research Communications, vol. 314, no. 4, pp. 1093–1099, 2004. View at Publisher · View at Google Scholar
  47. S. Hazra and S. M. Dubinett, “Ciglitazone mediates COX-2 dependent suppression of PGE2 in human non-small cell lung cancer cells,” Prostaglandins, Leukotrienes and Essential Fatty Acids, vol. 77, no. 1, pp. 51–58, 2007. View at Publisher · View at Google Scholar
  48. D. Chen, G. Jin, Y. Wang et al., “Genetic variants in peroxisome proliferator-activated receptor-? gene are associated with risk of lung cancer in a Chinese population,” Carcinogenesis, vol. 29, no. 2, pp. 342–350, 2008. View at Publisher · View at Google Scholar
  49. A. Amoruso, C. Bardelli, G. Gunella, L. G. Fresu, V. Ferrero, and S. Brunelleschi, “Quantification of PPAR-γ protein in monocyte/macrophages from healthy smokers and non-smokers: a possible direct effect of nicotine,” Life Sciences, vol. 81, no. 11, pp. 906–915, 2007. View at Publisher · View at Google Scholar
  50. V. K. Rehan, Y. Wang, S. Sugano et al., “In utero nicotine exposure alters fetal rat lung alveolar type II cell proliferation, differentiation, and metabolism,” American Journal of Physiology, vol. 292, no. 1, pp. L323–L333, 2007. View at Publisher · View at Google Scholar
  51. A. H. Limper and J. Roman, “Fibronectin. A versatile matrix protein with roles in thoracic development, repair and infection,” Chest, vol. 101, no. 6, pp. 1663–1673, 1992. View at Publisher · View at Google Scholar
  52. J. Roman, J. D. Ritzenthaler, A. Gil-Acosta, H. N. Rivera, and S. Roser-Page, “Nicotine and fibronectin, expression in lung fibroblasts: implications for tobacco-related lung tissue remodeling,” The FASEB Journal, vol. 18, no. 12, pp. 1436–1438, 2004. View at Publisher · View at Google Scholar
  53. S. Han, F. R. Khuri, and J. Roman, “Fibronectin stimulates non-small cell lung carcinoma cell growth through activation of Akt/mammalian target of rapamycin/S6 kinase and inactivation of LKB1/AMP-activated protein kinase signal pathways,” Cancer Research, vol. 66, no. 1, pp. 315–323, 2006. View at Publisher · View at Google Scholar
  54. S. Han, J. D. Ritzenthaler, S. V. Sitaraman, and J. Roman, “Fibronectin increases matrix metalloproteinase 9 expression through activation of c-Fos via extracellular-regulated kinase and phosphatidylinositol 3-kinase pathways in human lung carcinoma cells,” Journal of Biological Chemistry, vol. 281, no. 40, pp. 29614–29624, 2006. View at Publisher · View at Google Scholar
  55. S. Han, J. D. Ritzenthaler, H. N. Rivera, and J. Roman, “Peroxisome proliferator-activated receptor-γ ligands suppress fibronectin gene expression in human lung carcinoma cells: involvement of both CRE and Sp1,” American Journal of Physiology, vol. 289, no. 3, pp. L419–L428, 2005. View at Publisher · View at Google Scholar
  56. S. Han, H. N. Rivera, and J. Roman, “Peroxisome proliferator-activated receptor-γ ligands inhibit α5 integrin gene transcription in non-small cell lung carcinoma cells,” American Journal of Respiratory Cell and Molecular Biology, vol. 32, no. 4, pp. 350–359, 2005. View at Publisher · View at Google Scholar
  57. V. G. Keshamouni, D. A. Arenberg, R. C. Reddy, M. J. Newstead, S. Anthwal, and T. J. Standiford, “PPAR-γ activation inhibits angiogenesis by blocking ELR+CXC chemokine production in non-small cell lung cancer,” Neoplasia, vol. 7, no. 3, pp. 294–301, 2005. View at Publisher · View at Google Scholar
  58. I. K. Choi, Y. H. Kim, J. S. Kim, and J. H. Seo, “PPAR-γ ligand promotes the growth of APC-mutated HT-29 human colon cancer cells in vitro and in vivo,” Investigational New Drugs, vol. 26, no. 3, pp. 283–288, 2008. View at Publisher · View at Google Scholar
  59. E. Saez, J. Rosenfeld, A. Livolsi et al., “PPAR? signaling exacerbates mammary gland tumor development,” Genes & Development, vol. 18, no. 5, pp. 528–540, 2004. View at Publisher · View at Google Scholar
  60. S. Theocharis, H. Kanelli, E. Politi et al., “Expression of peroxisome proliferator activated receptor-gamma in non-small cell lung carcinoma: correlation with histological type and grade,” Lung Cancer, vol. 36, no. 3, pp. 249–255, 2002. View at Publisher · View at Google Scholar
  61. G. Muzio, A. Trombetta, M. Maggiora et al., “Arachidonic acid suppresses growth of human lung tumor A549 cells through down-regulation of ALDH3A1 expression,” Free Radical Biology and Medicine, vol. 40, no. 11, pp. 1929–1938, 2006. View at Publisher · View at Google Scholar
  62. I. Avis, A. Martínez, J. Tauler et al., “Inhibitors of the arachidonic acid pathway and peroxisome proliferator-activated receptor ligands have superadditive effects on lung cancer growth inhibition,” Cancer Research, vol. 65, no. 10, pp. 4181–4190, 2005. View at Publisher · View at Google Scholar
  63. C.-J. Yao, G.-M. Lai, C.-F. Chan, A.-L. Cheng, Y.-Y. Yang, and S.-E. Chuang, “Dramatic synergistic anticancer effect of clinically achievable doses of lovastatin and troglitazone,” International Journal of Cancer, vol. 118, no. 3, pp. 773–779, 2006. View at Publisher · View at Google Scholar
  64. R. A. Nemenoff and R. A. Winn, “Role of nuclear receptors in lung tumourigenesis,” European Journal of Cancer, vol. 41, no. 16, pp. 2561–2568, 2005. View at Publisher · View at Google Scholar
  65. G. D. Girnun, E. Naseri, S. B. Vafai et al., “Synergy between PPAR? ligands and platinum-based drugs in cancer,” Cancer Cell, vol. 11, no. 5, pp. 395–406, 2007. View at Publisher · View at Google Scholar
  66. 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
  67. C. D. Allred and M. W. Kilgore, “Selective activation of PPARγ in breast, colon, and lung cancer cell lines,” Molecular and Cellular Endocrinology, vol. 235, no. 1-2, pp. 21–29, 2005. View at Publisher · View at Google Scholar
  68. H. J. Kim, J.-Y. Hwang, H. J. Kim et al., “Expression of a peroxisome proliferator-activated receptor ?1 splice variant that was identified in human lung cancers suppresses cell death induced by cisplatin and oxidative stress,” Clinical Cancer Research, vol. 13, no. 9, pp. 2577–2583, 2007. View at Publisher · View at Google Scholar