15-Deoxy-Δ12,14-prostaglandin J2 induces growth inhibition, cell cycle arrest and apoptosis in human endometrial cancer cell lines

Li,Haili; Narahara,Hisashi

doi:10.3892/ijmm.2013.1268

15-Deoxy-Δ12,14-prostaglandin J2 induces growth inhibition, cell cycle arrest and apoptosis in human endometrial cancer cell lines

Authors:
- Haili Li
- Hisashi Narahara
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Affiliations: Department of Obstetrics and Gynecology, Oita University Faculty of Medicine, Yufu-shi, Oita, Japan
Published online on: February 5, 2013 https://doi.org/10.3892/ijmm.2013.1268
Pages: 778-788

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Abstract

15-Deoxy-∆12,14-prostaglandin J2 (15d-PGJ2), a peroxisome proliferator-activated receptor γ ligand, has been reported to have antiproliferative activity in certain types of cancer. The purpose of this study was to elucidate the effect of 15d-PGJ2 on endometrial cancer cells, as well as the mechanism of action. Endometrial cancer-derived cells (HHUA, Ishikawa and HEC-59) were treated with various concentrations of 15d-PGJ2, and its effects on cell growth, the cell cycle and apoptosis were investigated in vitro. Using cDNA microarrays, some potential targets of this drug were identified. All endometrial cancer cell lines were sensitive to the growth-inhibitory effect of 15d-PGJ2. Cell cycle arrest at the G2/M phase of the cell cycle and induction of apoptosis were observed. Concerning the gene expression changes induced by 15d-PGJ2 treatment, the upregulation of aldo-keto reductase family 1 member C3 (AKR1C3) and the downregulation of anterior gradient homolog 3 (AGR3) and nitric oxide synthase 2A (NOS2A) were confirmed using western blot analysis in all the cell lines examined. These results suggest that 15d-PGJ2 may be a novel therapeutic option for the treatment of endometrial cancer.

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1	Reinhardt MJ: Gynecologic tumors. Recent Results Cancer Res. 170:141–150. 2008. View Article : Google Scholar
2	Obel JC, Friberg G and Fleming GF: Chemotherapy in endometrial cancer. Clin Adv Hematol Oncol. 4:459–468. 2006.
3	Hill EK and Dizon DS: Medical therapy of endometrial cancer: current status and promising novel treatments. Drugs. 72:705–713. 2012. View Article : Google Scholar : PubMed/NCBI
4	Ota K, Ito K, Suzuki T, et al: Peroxisome proliferator-activated receptor gamma and growth inhibition by its ligands in uterine endometrial carcinoma. Clin Cancer Res. 12:4200–4208. 2006. View Article : Google Scholar
5	Xin B, Yokoyama Y, Shigeto T, Futagami M and Mizunuma H: Inhibitory effect of meloxicam, a selective cyclooxygenase-2 inhibitor, and ciglitazone, a peroxisome proliferator-activated receptor gamma ligand, on the growth of human ovarian cancers. Cancer. 110:791–800. 2007. View Article : Google Scholar
6	Yang YC, Tsao YP, Ho TC and Choung IP: Peroxisome proliferator-activated receptor-gamma agonists cause growth arrest and apoptosis in human ovarian carcinoma cell lines. Int J Gynecol Cancer. 17:418–425. 2007. View Article : Google Scholar : PubMed/NCBI
7	Nosjean O and Boutin JA: Natural ligands of PPARgamma: are prostaglandin J(2) derivatives really playing the part? Cell Signal. 14:573–583. 2002.PubMed/NCBI
8	Forman BM, Tontonoz P, Chen J, Brun RP, Spiegeiman BM and Evans RM: 15-Deoxy-delta 12, 14-prostaglandin J₂ is a ligand for the adipocyte determination factor PPARγ. Cell. 83:803–812. 1995.PubMed/NCBI
9	Kliewer SA, Lenhard JM, Willson TM, Patel I, Morris DC and Lehmann JM: A prostaglandin J₂ metabolite binds peroxisome proliferator-activated receptor g and promotes adipocyte differentiation. Cell. 83:813–819. 1995.PubMed/NCBI
10	Wang JJ and Mak OT: Induction of apoptosis in non-small cell lung carcinoma A549 cells by PGD₂ metabolite, 15d-PGJ₂. Cell Biol Int. 35:1089–1096. 2011. View Article : Google Scholar : PubMed/NCBI
11	Shin SW, Seo CY, Han H, et al: 15d-PGJ₂ induces apoptosis by reactive oxygen species-mediated inactivation of Akt in leukemia and colorectal cancer cells and shows in vivo antitumor activity. Clin Cancer Res. 15:5414–5425. 2009.PubMed/NCBI
12	Mansure JJ, Nassim R and Kassouf W: Peroxisome proliferator-activated receptor gamma in bladder cancer: a promising therapeutic target. Cancer Biol Ther. 8:6–15. 2009. View Article : Google Scholar : PubMed/NCBI
13	Beissbarth T and Speed TP: GOstat: find statistically overrepresented Gene Ontologies within a group of genes. Bioinformatics. 20:1464–1465. 2004. View Article : Google Scholar : PubMed/NCBI
14	Rimon G, Bazenet CE, Philpott KL and Rubin LL: Increased surface phosphatidylserine is an early marker of neuronal apoptosis. J Neurosci Res. 48:563–570. 1997. View Article : Google Scholar : PubMed/NCBI
15	Chen Y, Kramer DL, Diegelman P, Vujcic S and Porter CW: Apoptotic signaling in polyamine analogue-treated SK-MEL-28 human melanoma cells. Cancer Res. 61:6437–6444. 2001.PubMed/NCBI
16	Zakharov V, Lin HK, Azzarello J, et al: Suppressed expression of type 2 3alpha/type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) in endometrial hyperplasia and carcinoma. Int J Clin Exp Pathol. 3:608–617. 2010.PubMed/NCBI
17	Gray TA, MacLaine NJ, Michie CO, et al: Anterior Gradient-3: a novel biomarker for ovarian cancer that mediates cisplatin resistance in xenograft models. J Immunol Methods. 378:20–32. 2012. View Article : Google Scholar : PubMed/NCBI
18	Eyler CE, Wu Q, Yan K, et al: Glioma stem cell proliferation and tumor growth are promoted by nitric oxide synthase-2. Cell. 146:53–66. 2011. View Article : Google Scholar : PubMed/NCBI