Suppression of chondrosarcoma cells by 15-deoxy-Δ12,14- prostaglandin J2 is associated with altered expression of Bax/Bcl-xL and p21

Zheng Nan Shen, Keiichiro Nishida, Hideyuki Doi, Toshitaka Oohashi, Satoshi Hirohata, Toshifumi Ozaki, Aki Yoshida, Yoshifumi Ninomiya, Hajime Inoue

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40 Citations (Scopus)

Abstract

We previously reported that 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), the most potent agonist for peroxisome proliferator-activated receptor γ (PPARγ), induces apoptosis of human chondrosarcoma cell line OUMS-27. The current study aimed to explore the mechanism of 15d-PGJ2-induced apoptosis and inhibition of cell proliferation in OUMS-27 cells. The preliminary results of cDNA microarray analysis showed the down-regulation of anti-apoptotic Bcl-xL and up-regulation of pro-apoptotic Bax in the process of 15d-PGJ2-induced apoptosis. These changes were further confirmed at mRNA and protein levels by RT-PCR and Western blot analysis, respectively. Among cyclin-dependent kinase inhibitors, p21 was induced and up-regulated by 15d-PGJ2, but p16 and p27 were not changed, suggesting that the involvement of p21 in inhibition of cell proliferation. Activation of caspase-3 by 15d-PGJ2 was partly, but not completely, blocked by PPARγ antagonist (GW9662) suggesting the 15d-PGJ2 exerted its effect by PPARγ-dependent and -independent pathways. Interestingly, immunohistochemical study on human chondrosarcoma samples revealed that Bcl-xL is frequently expressed by tumor cells. The results of the current study suggest that the potential ability of 15d-PGJ2 in regulation of cell cycle and inhibition of Bcl-xL expression might be beneficial in the development of novel pharmacological agents for chondrosarcoma.

Original languageEnglish
Pages (from-to)375-382
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume328
Issue number2
DOIs
Publication statusPublished - Mar 11 2005

Keywords

  • 15d-PGJ
  • Apoptosis
  • Bcl-xL
  • Chondrosarcoma
  • PPARγ
  • p21

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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