77
Views
71
CrossRef citations to date
0
Altmetric
Review

Therapeutic potential of thiazolidinediones as anticancer agents

, , &
Pages 1925-1937 | Published online: 02 Mar 2005

Bibliography

  • SALTIEL AR, OLEFSKY Thiazolidinediones in the treatment of insulin resistance and Type II diabetes. Diabetes (1996) 45:1661–1669.
  • LEHMANN JM, MOORE LB, SMITH-OLIVER TA et al: An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor (PPAR-y). .1. Biol. Chem. (1995) 270:12953–12956.
  • •Identification of PPAR-y as the molecular target for TZDs.
  • WILLSON TM, BROWN PJ, STERNBACH DD, HENKE BR: The PPARs: from orphan receptors to drug discovery. Med. Chem. (2000) 43:527–550.
  • KOYAMA H, BOUERES JK, HAN Wet al.: 5-Aryl thiazolidine-2,4-diones as selective PPAR-gamma agonists. Bioorg. Med. Chem. Lett. (2003) 13:1801–1804.
  • CHANG AY, WYSE BM, GILCHRIST BJ, PETERSON T, DIANI AR: Ciglitazone, a new hypoglycemic agent. I. Studies in ob/ob and db/db mice, diabetic Chinese hamsters, and normal and streptozotocin-diabetic rats. Diabetes (1983) 32:830–838.
  • CANIGGIA I, GRISARU- GRAVNOSKY S, KULISZEWSKY M, POST M, LYE SJ: Inhibition of TGF-beta 3 restores the invasive capability of extravillous trophoblasts in preeclamptic pregnancies. Clin. Invest. (1999) 103:1641–1650.
  • ISSEMANN I, GREEN S: Activation of amember of the steroid hormone receptor superfamily by perwdsome proliferators. Nature (1990) 347:645–650.
  • BERGER J, MOLLER DE: Mechanism of action of PPARs. Ann. Rev Med. (2002) 53:409–435.
  • ••Excellent review on the molecularmechanisms of PPAR action and involvement of PPARs in chronic disease.
  • DEBRIL MB, RENAUD JP, FAJAS L, AUWERX J: The pleiotropic functions of peroxisome proliferator-activated receptor gamma. Ma Med. (2001) 79:30–47.
  • MANGELSDORF DJ, EVANS RM: The RXR heterodimers and orphan receptors. Cell (1995) 83:841–850.
  • LEMBERGER T, DESVERGNE B, WAHLI W: Perwdsome proliferator-activated receptors: a nuclear receptor signaling pathway in lipid physiology. Ann. Rev Cell. Dev. Biol. (1996) 12:335–363.
  • NOLAN JJ, LUDVIK B, BEERDSEN P,JOYCE M, OLEFSKY J: Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone. N Engl. J. Med. (1994) 331:1188–1193.
  • RICOTE M, LI AC, WILLSON TM, KELLY CJ, GLASS CK: The peroxisome proliferator-activated receptor-7 is a negative regulator of macrophage activation. Nature (1998) 391:79–82.
  • XIN X, YANG S, KOWALSKI J, GERRITSEN ME: Percodsome proliferator-activated receptor y ligands are potent inhibitors of angiogenesis M vitro and M vivo. J. Biol. Chem. (1999) 274:9116–9121.
  • PANIGRAHY D, SINGERS, SHEN LQ et al.: PPAR-y ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis. j Clin. Invest. (2002) 110:923–932.
  • •This paper shows that TZDs can target tumour endothelium.
  • LI AC, BROWN KK, SILVESTRE MJ et al.: Percodsome proliferator-activated receptor y ligands inhibit development of atheroclerosis in LDL receptor-deficient mice. J. Clin. Invest. (2000) 106:523–531.
  • FAHMI H, PELLETIER JP, MARTEL-PELLETIER J: PPAR-y ligands as modulators of inflammatory and catabolic responses in arthritis. An overview. Rheumatol. (2002) 29:3–14.
  • KLETZIEN RE CLARKE SD, ULRICH RG: Enhancement of adipocyte differentiation by an insulin-sensitizing agent. Mol. Pharmacol. (1992) 41:393–398.
  • TONTONOZ P, HUE, SPIEGELMAN BM: Stimulation of adipogenesis in fibroblasts by PPAR-y 2, a lipid activated transcription factor. Cell (1994) 79:1147–1156.
  • ••First experimental evidence that PPAR-yligands can induce differentiation in non-cancerous cells.
  • TONTONOZ P, HU E, GRAVES R, BUDAVARI A,SPIEGELMAN BM: mPPAR-y2: tissue-specific regulator of an adipocyte enhancer. Genes Dev. (1994) 8(10): 1224–1234.
  • SCHOONJANS K, PEINADO-ONSURBE J, LEFEBVRE AM et al.: PPAR-a and PPAR-y activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J. (1996) 15:5336–5348.
  • ROSEN ED, SPIEGELMAN BM: PPAR-ya nuclear regulator of metabolism, differentiation, and cell growth. J. Biol. Chem. (2001) 276:37731–37734.
  • BARAK Y, NELSON MC, ONG ES et al.:PPAR-y is required for placental, cardiac, and adipose tissue development. Mol. Cell (1999) 4:585–595.
  • TONTONOZ P, NAGY L, ALVAREZ JG, THOMAZY VA, EVANS RM: PPAR-y promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell (1998) 93:241–252.
  • MUELLER E, SARRAF P, TONTONOZ P et al.: Terminal differentiation of human breast cancer through PPAR-y. Mol. Cell. (1998) 1:465–470.
  • SARRAF P, MUELLER E, JONES D et al.: Differentiation and reversal of malignant changes in colon cancer through PPAR-y. Nat. Med. (1998) 4:1046–1052.
  • TONTONOZ P, SINGER S, FORMAN BM et al.: Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor y and the retinoid X receptor. Proc. Nati Acad. Sri. USA (1997) 94:237–241.
  • ••Elegant work showing that TTDs can induce differentiation of tumour cells.
  • MOTOMURA W, OKUMURA T, TAKAHASHI N, OBARA T, KOHGO Y: Activation of peroxisome proliferator-activated receptor gamma by troglitazone inhibits cell growth through the increase of p27Kipl in human pancreatic cells. Cancer Res. (2000) 60:5558–5564.
  • DUBOIS RN, GUPTA R, BROCKMAN J et al.: The nuclear eicosanoid receptor, PPAR-y, is aberrantly expressed in colonic cancers. Carcinogenesis (1998) 19:49–53.
  • TERASHITA Y, SASAKI H, HARUKI N et al.: Decreased peroxisome proliferator-activated receptor gamma gene expression is correlated with poor prognosis in patients with esophageal cancer. Jpn. Clin. Oncol. (2002) 32:238–243.
  • SASAKI H, TANAHASHI M, YUKIUE H et al.: Decreased perioxisome proliferator-activated receptor gamma gene expression was correlated with poor prognosis in patients with lung cancer. Lung Cancer (2002) 36:71–76.
  • HAUSER S, ADELMANT G, SARRAF P et al.: Degradation of the peroxisome proliferator-activated receptor y is linked to ligand dependent activation. Biol. Chem. (2000) 275:18527–18533.
  • WILLSON TM, COBB JE, COWAN DJ et al.: The structure-activity relationship between peroxisome proliferator-activated receptor gamma agonism and the antihyperglycemic activity of thiazolidinediones. Med. Chem. (1996) 39:665–668.
  • KOPELOVICH L, FAY JR, GLAZER RI, CROWELL JA: Peroxisome proliferator-activated receptor modulators as potential chemopreventive agents. Mol. Cancer Ther. (2002) 1:357–363.
  • KOEFFLER HP: Percodsome proliferator-activated receptor gamma and cancers. Clin. Cancer. Res. (2003) 9:1–9.
  • SMITH MR, KANTOFF PW: Percodsome proliferator-activated receptor gamma (PPAR-y) as a novel target for prostate cancer. Invest. New Drugs (2002) 20:195–200.
  • WARRELL RP Jr, FRANKEL SR, MILLER WH Jr et al.: Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). N. Engl. J. Med. (1991) 324:1385–1393.
  • ALTIOK S, XU M, SPIEGELMAN BM: PPAR-y induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A. Genes Dev. (1997) 11:1987–1998.
  • DEMETRI GD, FLETCHER CD, MUELLER E et al.: Induction of solid tumor differentiation by the peroxixome proliferator-activated receptor-7 ligand troglitazone in patients with liposarcoma. Proc. Natl. Acad. Sci. USA (1999) 96:3951–3956.
  • CHANG TH, SZABO E: Enhanced growth inhibition by combination differentiation therapy with ligands of peroxisome proliferator-activated receptor-gamma and inhibitors of histone deacetylase in adenocarcinoma of the lung. Clin. Cancer Res. (2002) 8:1206–1212.
  • CHANG T, SZABO E: Induction of differentiation and apoptosis by ligands of peroxisome proliferator-activated receptor y in non-small cell lung cancer. Cancer Res. (2000) 60:1129–1138.
  • HAYDON RC, ZHOU L, FENG T et al.: Nuclear receptor agonists as potential differentiation therapy agents for human osteosarcoma. Clin. Cancer Res. (2002) 8:1288–1294.
  • ELSTNER E, MULLER C, KOSHIZUKA K et al.: Ligands for peroxisome proliferator-activated receptor y and retinoic acid and receptor inhibit growth and induce apoptosis of human breast cancer cells M vitro and in BNX mice. Proc. Natl. Acad. Sci. USA (1998) 95:8806–8811.
  • KUBOTA T, KOSHIZUKA K, WILLAMSON EA et al.: Ligand for peroxisome-activated receptor y (troglitazone) has potent antitumor effect against human prostate cancer both in vivo and M vitro. Cancer Res. (1998) 58:3344–3352.
  • FAJAS L, AUBOEUF D, RASPE E et al: The organization, promoter analysis, and expression of the human PPAR-y gene. Biol. Chem. (1997) 272:18779–18789.
  • BROCKMAN JA, GUPTA RA, DUBOIS RN: Activation of PPAR-y leads to inhibition of anchorage-independent growth of human colorectal cancer cells. Gastroenterology (1998) 115:1049–1055.
  • KITAMURA S, MIYAZAKI Y, SHINOMURA Y et al.: Peroxisome proliferator-activated receptor gamma induces growth arrest and differentiation markers of human colon cancer cells. fpn..1. Cancer Res. (1999) 90:75–80.
  • SU CG, WEN X, BAILEY ST et al: A novel therapy for colitis utilizing PPAR-y ligands to inhibit the epithelial inflammatory response. Clin. Invest. (1999) 104:383–389.
  • TANAKA T, KOHNO H, YOSHITANI S et al: Ligands for peroxisome proliferator-activated receptors a and y inhibit chemically induced colitis and formation of aberrant crypt foci in rats. Cancer Res. (2001) 61:2424–2428.
  • OSAWA E, NAKAJIMA A, WADA K et al: Percodsome proliferator-activated receptor gamma ligands suppress colon carcinogenesis induced by azoxymethane in mice. Gastroenterology (2003) 124:361–367.
  • SAEZ E, TONTONOZ P, NELSON MC et al: Activators of the nuclear receptor PPAR-y enhance colon polyp formation. Nat. Med. (1998) 4:1058–1061.
  • LEFEBVRE AM, CHEN I, DESREUMAUX P et al.: Activation of the peroxisome proliferator-activated receptor y promotes the development of colon tumors in C57BL/6J-APCmEril+ mice. Nat. Med. (1998) 4(9):1053–1057.
  • GIRNUN GD, SMITH WM, DRORI S et al.: APC-dependent suppression of colon carcinogenesis by PPAR-gamma. Proc. Natl. Acad. Sci. USA. (2002) 99:13771–13776.
  • •These studies suggest an important use for TZDs as chemopreventative agents in colon cancer.
  • CLAY CE, NAMEN AM, ATSUMI G et al.: Influence of J series prostaglandins on apoptosis and tumorigenesis of breast cancer cells. Carcinogenesis (1999) 20:1905–1911.
  • BUTLER R, MITCHELL SH, TINDALL DJ, YOUNG CY: Nonapoptotic cell death associated with S-phase arrest of prostate cancer cells via the peroxisome proliferator-activated receptor gamma ligand, 15-deoxy-delta12,14-prostaglandin J2. Cell Growth Differ. (2000) 11:49–61.
  • MEHTA RG, WILLIAMSON E, PATEL MK, KOEFFLER HP: A ligand of peroxisome proliferator-activated receptor gamma, retinoids, and prevention of preneoplastic mammary lesions. Natl. Cancer Inst. (2000) 92:418–423.
  • ••This is the first report that TZDs may havechemopreventative activity.
  • PIGHETTI GM, NOVOSAD W, NICHOLSON C et al.: Therapeutic treatment of DMBA-induced mammary tumors with PPAR ligands. Anticancer Res. (2001) 21:825–829.
  • RUBIN GL, ZHAO Y, KALUS AM, SIMPSON ER: Percodsome proliferator-activated receptor gamma ligands inhibit estrogen biosynthesis in human breast adipose tissue: possible implications for breast cancer therapy. Cancer Res. (2000) 60:1604–1608.
  • MUELLER E, SMITH M, SARRAF P et al.: Effects of ligand activation of peroxisome proliferator-activated receptor yin human prostate cancer. Proc. Natl. Acad. Sci. USA (2000) 97:10990–10995.
  • SHAPPELL SB, GUPTA RA, MANNING S et al: 15S- Hydroxyeicosatetraenoic acid activates peroxisome proliferator-activated receptor gamma and inhibits proliferation in PC3 prostate carcinoma cells. Cancer Res. (2001) 61:497–503.
  • GUAN YE ZHANG YH, BREYER PM, DAVIS L, BREYER MD: Expression of peroxisome proliferator-activated receptor gamma (PPAR-gamma) in human transitional bladder cancer and its role in inducing cell death. Neoplasia (1999) 1:330–339.
  • NAKASHIRO K, HAYASHI Y, KITA A et al: Role of peroxisome proliferator-activated receptor y and its ligands in non-neoplastic and neoplastic human urothelial cells. Am. .1. Pathol (2001) 159:591–597.
  • YOSHIMURA R, MATSUYAMA M, SEGAWA Yet al.: Expression of peroxisome proliferator-activated receptors (PPARs) in human urinary bladder carcinoma and growth inhibition by its agonists. Int. .1. Cancer (2003) 104:597–602.
  • KATO M, NAGAYA T, FUJIEDA M et al:Expression of PPAR-y and its ligand-dependent growth inhibition in human brain tumor cell lines. fpn. I Cancer. Res. (2002) 93:660–666.
  • KEELAN JA, SATO TA, MARVIN KW et al.: 15-Deoxy-delta (12, 14) -prostaglandin J(2), a ligand for peroxisome proliferator-activated receptor-gamma, induces apoptosis in JEG3 choriocarcinoma cells. Biotbem. Biophys. Res. Commun. (1999) 262:579–585.
  • NISHIDA K, FURUMATSU T, TAKADA I et al: Inhibition of human chondrosarcoma cell growth via apoptosis by peroxisome proliferator-activated receptor-gamma. Br. I Cancer (2002) 86:1303–1309.
  • TAKASHIMA T, FUJIWARA Y, HIGUCHI K et al.: PPAR-y ligands inhibit growth of human esophageal adenocarcinoma cells through induction of apoptosis, cell cycle arrest and reduction of ornithine decarboxylase activity. Int. Oncol (2001) 19:465–471.
  • RUMI MA, SATO H, ISHIHARA Set al.: Growth inhibition of esophageal squamous carcinoma cells by peroxisome proliferator-activated receptor-gamma ligands. I Lab. Clin. Med. (2002) 140:17–26.
  • TAKAHASHI N, OKUMURA T, MOTOMURA W et al: Activation of PPAR-y inhibits cell growth and induces apoptosis in human gastric cancer cells. FEBS Lett. (1999) 455:135–139.
  • SATO H, ISHIHARA S, KAWASHIMA K et al.: Expression of peroxisome proliferator-activated receptor (PPAR)-y in gastric cancer and inhibitory effects of PPAR-y agonists. Br. I Cancer. (2000) 83:1394–1400.
  • FUJIMURA S, SUZUMIYA J, NAKAMURA K, ONO J: Effects of troglitazone on the growth and differentiation of hematopoietic cell lines. Int.I Oncol (1998) 13:1263–1267.
  • SUGIMURA A, KIRIYAMA Y, NOCHI H et al.: Troglitazone suppresses cell growth of myeloid leukemia cell lines by induction of p21WAF1/CIP 1 cyclin-dependent kinase inhibitor. Biochem. Biophys. Res. Commun. (1999) 261:833–837.
  • ASOU H, VERBEEK W, WILLIAMSON E et al: Growth inhibition of myeloid leukemia cells by troglitazone, a ligand for peroxisome proliferator activated receptor gamma, and retinoids. Int.' Oncol (1999) 15:1027–1031.
  • HIRASE N, YANASE T, MU Y et al.: Thiazolidinedione induces apoptosis and monocytic differentiation in the promyelocytic leukemia cell line HL60. Oncology (1999) 57\(Suppl. 2):17–26.
  • HIRASE N, YANASE T, MU Y et al.: Thiazolidinedione suppresses the expression of erythroid phenotype in erythroleukemia cell line K562. Leak. Res. (2000) 24:393–400.
  • RUMI MA, SATO H, ISHIHARA S et al:Perwdsome proliferator-activated receptor gamma ligand-induced growth inhibition of human hepatocellular carcinoma. Br. .1. Cancer. (2001) 15:1640–1647.
  • TSUBOUCHI Y, SANO H, KAWAHITO Y et al.: Inhibition of human lung cancer cell growth by the peroxisome proliferator-activated receptor-gamma agonists through induction of apoptosis. Biochem. Biophys. Res. Commun. (2000) 270:400–405.
  • MOSSNER R, SCHULZ U, KRUGER U et al: Agonists of peroxisome proliferator-activated receptor gamma inhibit cell growth in malignant melanoma. J. Invest. Dermatol (2002) 119:576–582.
  • ITAMI A, WATANABE G, SHIMADA Y et al.: Ligands for peroxisome proliferator-activated receptor gamma inhibit growth of pancreatic cancers both M vitro and in vivo. Int. J. Cancer (2001) 94:370–376.
  • HEANEY AP, FERNANDO M, MELMED S: PPAR-y receptor ligands: novel therapy for pituitary adenomas. J. Clin. Invest. (2003) 111:1381–1888.
  • INOUE K, KAWAHITO Y, TSUBOUCHI Y et al.: Expression of peroxisome proliferator-activated receptor gamma in renal cell carcinoma and growth inhibition by its agonists. Biochem. Biophys. Res. Commun. (2001) 287:727–732.
  • HASE T, YOSHIMURA R, MITSUHASHI M et al.: Expression of peroxisome proliferator-activated receptors in human testicular cancer and growth inhibition by its agonists. Urology (2002) 60:542–547.
  • OHTA K, ENDO T, HARAGUCHI K, HERSHMAN JM,ONAYA T: Ligands for peroxisome proliferator-activated receptor y inhibit growth and induce apoptosis of human papillary thyroid carcinoma cells. .1. Clin. Endocrinol Metab. (2001) 86:2170–2177.
  • TSIBRIS JC, PORTER KB, JAZAYERI A et al.: Human uterine leiomyomata express higher levels of peroxisome proliferator-activated receptor y, retinoid X receptor a, and all-trans retinoic acid than myometrium. Cancer Res. (1999) 59:5737–5744.
  • NOLTE RT, WISELY GB, WESTIN S et al.: Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma. Nature (1998) 395:137–143.
  • MIZUKAMI J,TANIGUCHI T: The antidiabetic agent thiazolidinedione stimulates the interaction between PPAR-y and CBP. Biochem. Biophys. Res. Commun. (1997) 240:61–64.
  • PEARSON SL, CAWTHORNE MA, CLAPHAM JC et al: The thiazolidinedione insulin sensitiser, BRL 49653, increases the expression of PPAR-y and aP2 in adipose tissue of high-fat-fed rats. Biochem. Biophys. Res. Commun. (1996) 229:752–757.
  • MARTIN G, POIRIER H, HENNUYER N et al.: Induction of the fatty acid transport protein 1 and acyl-CoA synthase genes by dimer-selective rexinoids suggests that the peroxisome proliferator-activated receptor-retinoid X receptor heterodimer is their molecular target. J. Biol. Chem. (2000) 275:12612–12618.
  • CHAWLA A, BARAK Y, NAGY Let al.: PPAR-gamma dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation. Nat. Med. (2001) 7:48–52.
  • GERI-TOLD DL, LIUF, JIANG G et al: Gene expression profile of adipocyte differentiation and its regulation by peroxisome proliferator-activated receptor-gamma agonists. Endocrinology (2002) 143:2106–2118.
  • GUPTA RA, SARRAF P, BROCKMAN JA et al.: Peroxisome proliferator-activated receptor gamma and transforming growth factor-beta pathways inhibit intestinal epithelial cell growth by regulating levels of TSC-22. J. Biol. Chem. (2003) 278:7431–7438.
  • GUPTA RA, BROCKMAN JA, SARRAF P, WILLSON TM, DUBOIS RN: Target genes of peroxisome proliferator-activated receptor gamma in colorectal cancer cells. J. Biol. Chem. (2001) 276:29681–29687.
  • BURGERMEISTER E, TENCER L, LISCOVITCH M: Percodsome proliferator-activated receptor-gamma upregulates caveolin-1 and caveolin-2 expression in human carcinoma cells. Oncogene (2003) 22:3888–3900.
  • XU Y, IYENGAR S, ROBERTS RL, SHAPPELL SB, PEEHL DM: Primary culture model of peroxisome proliferator-activated receptor gamma activity in prostate cancer cells. J. Cell Physiol. (2003) 196:131–143.
  • MUELLER E, FEBBO P, SARRAF P et al.:Identification of PPAR-y specific target genes in prostate cancer. American Association for Cancer Research Annual Meeting, San Francisco, CA, USA (2002) (Abstract 605).
  • WRIGHT HM, CLISH CB, MIKAMI T et al.: A synthetic antagonist for the peroxisome proliferator-activated receptor gamma inhibits adipocyte differentiation. J. Biol. Chem. (2000) 275:1873–1877.
  • NAGAMINE M, OKUMURA T, TANNO S et al.: PPAR-y ligand-induced apoptosis through a p53-dependent mechanism in human gastric cancer cells. Cancer Sci. (2003) 94:338–343.
  • ZANDER T, KRAUS JA, GROMMES C et al.: Induction of apoptosis in human and rat glioma by agonists of the nuclear receptor PPAR-y. Neurochem. (2002) 81:1052–1060.
  • KITAMURA S, MIYAZAKI Y, HIRAOKA S et al.: PPAR-yagonists inhibit cell growth and suppress the expression of cyclin D1 and EGF-like growth factors in ras-transformed rat intestinal epithelial cells. Int. J. Cancer (2001) 94:335–342.
  • TAKEUCHI S, OKUMURA T, MOTOMURA W et al.: Troglitazone induces G1 arrest by p27 (Kip 1 ) induction that is mediated by inhibition of proteasome in human gastric cancer cells. fpn. J. Cancer Res. (2002) 93:774–782.
  • YOSHIZAWA K, CIOCA DP, KAWA S, TANAKA E, KIYOSAWA K: Peroxisome proliferator-activated receptor gamma ligand troglitazone induces cell cycle arrest and apoptosis of hepatocellular carcinoma cell lines. Cancer (2002) 95:2243–2251.
  • CHUNG SH, ONODA N, ISHIKAWA T et al.: Peroxisome proliferator-activated receptor gamma activation induces cell cycle arrest via the p53-independent pathway in human anaplastic thyroid cancer cells. fpn J. Cancer Res. (2002) 93:1358–1365.
  • YIN F, WAKINO S, LIU Z et al.: Troglitazone inhibits growth of MCF-7 breast carcinoma cells by targeting G1 cell cycle regulators. Biochem. Biophys. Res. Commun. (2001) 286:916–922.
  • TOYOTA M, MIYAZAKI Y, KITAMURA S et al: Peroxisome proliferator-activated receptor gamma reduces the growth rate of pancreatic cancer cells through the reduction of cyclin Dl. Life Sci. (2002) 70:1565–1575.
  • HAN C, DEMETRIS AJ, MICHALOPOULOS GK et al.: PPAR-y ligands inhibit cholangiocarcinoma cell growth through p53-dependent GADD45 and p21 pathway. Hepatology (2003) 38:167–177.
  • STAELS B, KOENIG W, HABIB A et al: Activation of human aortic smooth-muscle cells is inhibited by PPAR-a but not by PPAR-y activators. Nature (1998) 393:790–793.
  • GOKE R, GOKE A, GOKE B, CHEN Y: Regulation of TRAIL-induced apoptosis by transcription factors. Cell. Immunol. (2000) 201:77–82.
  • GUPTA RA, SARRAF P, MUELLER E et al.: Peroxisome proliferator-activated receptor gamma-mediated differentiation: a mutation in colon cancer cells reveals divergent and cell type-specific mechanisms. Biol. Chem. (2003) 278:22669–22677.
  • PATEL L, PASS I, COXON P et al.: Tumor suppressor and anti-inflammatory actions of PPAR-y agonists are mediated via upregulation of PTEN. Curt: Biol. (2001) 11:764–768.
  • FARROW B, EVERS BM: Activation of PPAR-y increases PTEN expression in pancreatic cancer cells. Biochem. Biophys. Res. Commun. (2003) 301:50–53.
  • AKTAS H, FLUCKIGER R, ACOSTA JA et al.: Depletion of intracellular Ca2+ stores, phosphorylation of eIF2a, and sustained inhibition of translation initiation mediate the anticancer effects of clotrimazole. Proc. Nati Acad. ScL USA. (1998) 95:8280–8285.
  • PALAKURTHI SS, AKTAS H, GRUBISSICH LM, MORTENSEN RIVI,HALPERIN JA: Anticancer effects of thiazolidinediones are independent of perwdsome proliferator-activated receptor y and mediated by inhibition of translation initiation. Cancer Res. (2001) 61:6213–6218.
  • •Studies identifying a novel PPAR-y-independent mechanism for the anticancer properties of TZDs with important clinical implications.
  • BAEK SJ, WILSON LC, HSI LC, ELING TE: Troglitazone, a peroxisome proliferator-activated receptor gamma (PPAR- y) ligand, selectively induces the early growth response-1 gene independently of PPAR- y. A novel mechanism for its anti-tumorigenic activity. Biol. Chem. (2003) 278:5845–5853.
  • BERGER J, LEIBOWITZ MD, DOEBBER TW et al.: Novel perwdsome proliferator-activated receptor (PPAR) gamma and PPAR delta ligands produce distinct biological effects. J. Biol. Chem. (1999) 274:6718–6725.
  • FOLKMAN J: Tumor angiogenesis. In: Cancer Medicine. JF Holland, El Frei, RCJ Bast, DW Kufe, RE Pollock and RR Weichselbaum (Eds), B. C. Decker, Inc, Ontario, Canada (2000):132–152.
  • MARX N, BOURCIER T, SUKHOVA GK, LIBBY P, PLUTZKY J: PPAR-y activation in human endothelial cells increases plasminogen activator inhibitor type-1 expression: PPAR-y as a potential mediator in vascular disease. Arterioscier. a/MA V3SC. Biol. (1999) 19:546–551.
  • BISHOP-BAILEY D, HLA T: Endothelial cell apoptosis induced by the perwdsome proliferator-activated receptor (PPAR) ligand 15-deoxy-prostaglandin J2. / Biol. Chem. (1999) 274:17042–17048.
  • GRALINSKI MR, ROWSE PE, BREIDER MA: Effects of troglitazone and pioglitazone on cytokine-mediated endothelial cell proliferation in vitro. Cardiovasc. Pharmacol (1998) 31:909–913.
  • GOETZE S, BUNGENSTOCK A, CZUPALLA C et al.: Leptin induces endothelial cell migration through Akt, which is inhibited by PPAR-y-ligands. Hypertension (2002) 40:748–754.
  • GOETZE S, EILERS F, BUNGENSTOCK A et al.: PPAR activators inhibit endothelial cell migration by targeting Mt. Biochem. Biol. Res. Comm. (2002) 293:1431–1437.
  • MURATA T, HE S, HANGAI M et al.: Peroxisome proliferator-activated receptor-y ligands inhibit choroidal neovascularization. Invest. Ophthalmol Vis. Sci. (2000) 41:2309–2317.
  • MURATA T, HATA Y, ISHIBASHI T et al.: Response of experimetal retinal neovascularization to thiazolidinediones. Arch. Ophthalmol (2001) 119:709–717.
  • INOUE K, KAWAHITO Y, TSUBOUCHI Y et al.: Expression of perwdsome proliferator-activated receptor (PPAR) gamma in human lung cancer. Anti-Cancer Res. (2001) 21(4A):2471–2476.
  • INOUE K, KAWAHITO Y, SANO H, TAKANO H, YOSHIKAWA T: New diagnostic tool for tumor angiogenesis. Chest (2003) 123:966–967.
  • LUCARELLI E, SANGIORGI L, MAINI V et al.: Troglitazione affects survival of human osteosarcoma cells. Int. Cancer (2002) 98:344–351.
  • FAUCONNET S, LASCOMBE I, CHABANNES E et al.: Differential regulation of vascular endothelial growth factor expression by perwdsome proliferator-activated receptors in bladder cancer cells. I. Biol. Chem. (2002) 277:23534–23543.
  • SIETTA-HONIGMANN MR, NATH AK, MURAKAMI C et al.: Biological action of leptin as an angiogenic factor. Science (1998) 281:1683–1686.
  • ZHANG M, VOLPERT 0, SHI YH, BOUCK N: Maspin is an angiogenesis inhibitor. Nat. Med. (2000) 6:196–199.
  • JIMENEZ B, VOLPERT OV, CRAWFORD SE et al: Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1. Nat. Med. (2000) 6:41–48.
  • HUANG H, CAMPBELL S, NELIUS T et al.: PPAR-y ligands improve anti-tumorigenic and anti-angiogenic efficacy of thrombospondin-1 through modulating its receptor CD36. New Directions M Angiogenesis Research meeting, Chicago, IL, USA (2003) (Abstract 15).
  • HISATAKE J, IKEZOE T, CAREY M et al.: Down-regulation of prostate-specific antigen expression by ligands for peroxisome proliferator-activated receptor yin human prostate cancer. Cancer Res. (2000) 60:5494–5498.
  • KULKE MH, DEMETRI GD, SHARPLESS NE et al.: A Phase II study of troglitazone, an activator of the PPAR-y receptor, in patients with chemotherapy-resistant metastatic colorectal cancer. Cancer (2002) 8:395–399.
  • BURSTEIN HJ, DEMETRI GD, MUELLER E et al: Use of the peroxisome proliferator-activated receptor (PPAR-) gamma ligand troglitazone as treatment for refractory breast cancer: a Phase II study. Breast Cancer Res. Treat. (2003) 79:391–397.
  • NEUSCHWANDER-TETRI BA, ISLEY WL, OKI JC et al: Troglitazone-induced hepatic failure leading to liver transplantation. A case report. Ann. Intern. Med. (1998) 129:38–41.
  • GOLDSTEIN BJ: Differentiating members of the thiazolidinedione class: a focus on efficacy. Diabetes Metab. Res. Rev (2002) 18\(Suppl. 2):S16–S22.
  • SMITH M: Rosiglitazone versus placebo for men with prostate cancer and a rising PSA after radical prostatectomy and/or radiation therapy. American Socieo, of Clinical Oncology Chicago, IL, USA (2003) (Abstract 1588).
  • DEBROCK G, VANHENTENRIJK V, SCIOT R et al.: A Phase II trial with rosiglitazone in liposarcoma patients. Br. J. Cancer (2003) 89:1409–1412.
  • •One of the first clinical evaluations of rosigjitazone treatment in cancer patients.
  • ESPOSTI RD, SCOPECE L, CAVALLO G et al.: Medical management of unresectable, recurrent retroperitoneal liposacroma (LS) with peroxisome proliferator-activated receptor (PPAR-y) ligands. American Socieo, of Clinical Oncology Chicago, IL, USA (2003) (Abstract 3338).
  • BROWDER T, BUTTERFIELD CE, KRALING BM et al: Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res. (2000) 60:1878–1886.
  • •First demonstration that chemotherapy on an antiangiogenic schedule combined with an angiogenesis inhibitor can regress experimental drug-resistant cancer.
  • KLEMENT G, BARUCHEL S, RAK J et al.: Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. Clin. Invest. (2000) 105:15–24.
  • BOGDAHN U, HAU P, JAUCH T et al: Low-dose chemotherapy in combination with COX-2 inhibitors and PPAR-gamma agonists in recurrent high grade glioma - a Phase II study. American Socieo, of Clinical Oncology Chicago, IL, USA (2003) (Abstract 473).
  • GOLDSTEIN BJ: Rosiglitazone. hat. Clin. Bract. (2000) 54:333–337.
  • KRENTZ AJ, BAILEY CJ, MELANDER A: Thiazolidinediones for Type 2 diabetes. New agents reduce insulin resistance but need long term clinical trials. Br. Med. (2000) 321:252–253.
  • LEESNITZER LM, PARKS DJ, BLEDSOE RK et al: Functional consequences of cysteine modification in the ligand binding sites of peroxisome proliferator activated receptors by GW9662. Biochemistry (2002) 41:6640–6650.
  • BRUEMMER D, BERGER JP, LIU J et al: A non-thiazolidinedione partial peroxisome proliferator-activated receptor gamma ligand inhibits vascular smooth muscle cell growth. Eur: j Pharmacol (2003) 466:225–234.
  • CLAY CE, NAMEN AM, ATSUMI G et al.: Magnitude of peroxisome proliferator-activated receptor-gamma activation is associated with important and seemingly opposite biological responses in breast cancer cells. Investig. Med. (2001) 49:413–420.
  • FREED MI, ALLEN A, JORKASKY DK, DICICCO RA: Systemic exposure to rosiglitazone is unaltered by food. Lim Clin. Pharmacol (1999) 55:53–56.
  • SLATON JW, PERROTTE P, INOUE K, DINNEY C, FIDLER IJ: Interferon-a-mediated down-regulation of angiogenesis-related genes and therapy of bladder cancer are dependent on optimization of biological dose and schedule. Gin. Cancer Res. (1999) 5:2726–2734.
  • JAMES SY, LINE, KOLLURI SK, DAWSON MI, ZHANG XK: Regulation of retinoic acid receptor beta expression by peroxisome proliferator-activated receptor gamma ligands in cancer cells. Cancer Res. (2003) 63:3531–3538.
  • FOLKMAN J: Angiogenesis. In: Harrison's Textbook of Internal Medicine E Braunwald, AS Fauci, DL Kasper, SL Hauser, DL Longo, JL Jameson (Eds), McGraw-Hill, New York (2001):517–530.
  • LI MY, DENG H, ZHAO JM, DAI D, TAN XY: Perwdsome proliferator-activated receptor gamma ligands inhibit cell growth and induce apoptosis in human liver cancer BEL-7402 cells. World j Castroenterol (2003) 9: 1683-1688.
  • MARTELLI ML, IULIANO R, LE PERA I et al.: Inhibitory effects of peroxisome poliferator-activated receptor gamma on thyroid carcinoma cell growth. Clin. Endocrinol. Metab. (2002) 87:4728–4735.
  • HOUSTON KD, COPLAND JA, BROADDUS RR et al.: Inhibition of proliferation and estrogen receptor signaling by peroxisome proliferator-activated receptor gamma ligands in uterine leiomyoma. Cancer Res. (2003) 63:1221–1227.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.