PPARgamma ligand (thiazolidinedione) induces growth arrest and differentiation markers of human pancreatic cancer cells.

Elnemr, Ayman; Ohta, Tetsuo; Iwata, Kazuya; Ninomia, Itasu; Fushida, Sachio; Nishimura, Genichi; Kitagawa, Hirohisa; Kayahara, Masato; Yamamoto, Miyuki; Terada, Tadashi; Miwa, Koichi

doi:10.3892/ijo.17.6.1157

Cited by 47 publications

(47 citation statements)

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“…Cells expressing nuclear p21 WAF1/CIP1 were subsequently arrested in G 0 -G 1 phase of the cell cycle. p21 WAF1/CIP1 has been implicated as a modulator of PPARg-mediated inhibition of cell proliferation but this was correlative in nature (Chang and Szabo, 2000;Elnemr et al, 2000;Koga et al, 2001;Hong et al, 2004). Our data indicated that in large part the antiproliferative activity of RS5444 is mediated through the upregulation of p21 WAF1/CIP1 in ATC tumors.…”

Section: Discussionmentioning

confidence: 68%

Novel high-affinity PPARγ agonist alone and in combination with paclitaxel inhibits human anaplastic thyroid carcinoma tumor growth via p21WAF1/CIP1

et al. 2005

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Peroxisomeproliferator-activated receptor gamma (PPARc) agonists demonstrate antitumor activity likely through transactivating genes that regulate cell proliferation, apoptosis, and differentiation. The PAX8/PPARc fusion oncogene, which is common in human follicular thyroid carcinomas appears to act via dominant negative suppression of wild-type PPARc, suggesting that it may be a tumor suppressor gene in thyroid cells. We have identified a novel high-affinity PPARc agonist (RS5444) that is dependent upon PPARc for its biological activity. This is the first report of this molecule and its antitumor activity. In vitro, the IC 50 for growth inhibition is B0.8 nM while anaplastic thyroid carcinoma (ATC) tumor growth was inhibited threeto fourfold in nude mice. siRNA against PPARc and a pharmacological antagonist demonstrated that functional PPARc was required for growth inhibitory activity of RS5444. RS5444 upregulated the cell cycle kinase inhibitor, p21 WAF1/CIP1 . Silencing p21 WAF1/CIP1 rendered cells insensitive to RS5444. RS5444 plus paclitaxel demonstrated additive antiproliferative activity in cell culture and minimal ATC tumor growth in vivo. RS5444 did not induce apoptosis but combined with paclitaxel, doubled the apoptotic index compared to that of paclitaxel. Our data indicate that functional PPARc is a molecular target for therapy in ATC. We demonstrated that RS5444, a thiazolidinedione (Tzd) derivative, alone or in combination with paclitaxel, may provide therapeutic benefit to patients diagnosed with ATC.

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Section: Discussionmentioning

confidence: 68%

Novel high-affinity PPARγ agonist alone and in combination with paclitaxel inhibits human anaplastic thyroid carcinoma tumor growth via p21WAF1/CIP1

et al. 2005

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“…57 It has been demonstrated that glitazones and troglitazone induced p21 with cell cycle arrest in G 1 phase in pancreatic tumor cell lines. 58,59 Itami et al 60 and Motomura et al 61 described upregulation of p27 in pancreatic tumors after treatment with PPARγ agonists. Furthermore, PPARγ agonists promote cell cycle arrest by the downregulation of cyclin D1 in several tumour cell lines, including those derived from pancreatic cancer, 60 breast tumours, 62 hepatocellular carcinoma 56 and NSCLC.…”

Section: Role In Cancer Biologymentioning

confidence: 99%

Peroxisome proliferator-activated receptor γ in bladder cancer: A promising therapeutic target

Mansure¹,

Nassim²,

Kassouf³

2009

Cancer Biology & Therapy

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“…Recent studies reported that 15-deoxy-D 12,14 -prostaglandin J 2 (15d-PGJ 2 ), the most potent endogenous ligand for PPARg, and the synthetic PPARg ligand thiazolidinedione (TZD) can induce terminal differentiation and growth inhibition of human liposarcoma (Tontonoz et al, 1997), breast (Elstner et al, 1998;Yee et al, 1999), prostate (Kubota et al, 1998), colon (Sarraf et al, 1998;Kitamura et al, 1999), gastric (Takahashi et al, 1999;Sato et al, 2000), lung (Chang and Szabo, 2000;Tsubouchi et al, 2000), and pancreas (Motomura et al, 2000;Elnemr et al, 2000) cancer cells, as well as hepatoma cells (Koga et al, 2001) in vitro and in vivo. The in vivo induction of histological and biochemical differentiation of liposarcomas by clinical trial of troglitazone administration was reported by Demetri et al (1999).…”

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confidence: 99%

Inhibition of human chondrosarcoma cell growth via apoptosis by peroxisome proliferator-activated receptor-γ

et al. 2002

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A rare immunohistochemical study using 28 surgical sections of human chondrosarcoma revealed that 67.9% of tumour cells had weak (10-40%) or strong (440%) positive immunoreaction for peroxisome proliferator-activated receptor-g. The expression of peroxisome proliferator-activated receptor-g mRNA and protein in human chondrosarcoma cell line OUMS-27 was also determined by reverse transcription-polymerase chain reaction and immunocytochemistry, respectively. Furthermore, the effects of peroxisome proliferator-activated receptor-g ligands on cell proliferation and survival were investigated in OUMS-27 cells. Pioglitazone, a selective ligand for peroxisome proliferator-activated receptor-g, and 15-deoxy-D 12,14 -prostaglandin J 2 (15d-PGJ 2 ), a putative endogenous ligand for peroxisome proliferator-activated receptor-g, inhibited the proliferation of OUMS-27 cells in a dose-dependent manner. The mechanism of cytotoxic effects of 15d-PGJ 2 was via apoptosis as shown by DNA fragmentation using TUNEL stain and DNA ladder formation, and by ultrastructural analysis using transmission electron microscopy. Flow-cytometric analysis using annexin-V-fluorescein and propidium iodide detected the early change of apoptosis, as well as necrosis of OUMS-27 cells at 4 h after co-incubation with 15d-PGJ 2 . These results suggest that peroxisome proliferator-activated receptor-g may play a significant role in the pathogenesis of chondrosarcoma, and peroxisome proliferatoractivated receptor-g ligands, especially 15d-PGJ 2 , may be of therapeutic value in the treatment of human chondrosarcoma.

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PPARgamma ligand (thiazolidinedione) induces growth arrest and differentiation markers of human pancreatic cancer cells.

Cited by 47 publications

References 0 publications

Novel high-affinity PPARγ agonist alone and in combination with paclitaxel inhibits human anaplastic thyroid carcinoma tumor growth via p21WAF1/CIP1

Novel high-affinity PPARγ agonist alone and in combination with paclitaxel inhibits human anaplastic thyroid carcinoma tumor growth via p21WAF1/CIP1

Peroxisome proliferator-activated receptor γ in bladder cancer: A promising therapeutic target

Inhibition of human chondrosarcoma cell growth via apoptosis by peroxisome proliferator-activated receptor-γ

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