Antitumor activity and downregulation of pro-angiogenic molecules in human prostate cancer cells by a novel thiazolidione compound

Fuminori Teraishi, Shuhong Wu, Satoshi Inoue, Lidong Zhang, John J. Davis, Wei Guo, Fengqin Dong, Bingliang Fang

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

BACKGROUND. Current treatments for prostate cancer are effective in many patients with locally advanced disease, but many of these patients eventually have recurrence. It is therefore important to develop alternative therapeutic agents with improved efficacy and tolerability. We recently identified a synthetic thiazolidin compound, 5-(2,4-dihydroxybenzylidene)-2-(phenylimino)-1, 3-thiazolidione (DBPT), that induces apoptosis in human colon cancer cells, independent of p53 and P-glycoprotein status. Here, we investigated the antitumor properties and mechanisms of action of this compound in human prostate cancer cell lines. METHODS. The effect of DBPT on cell-cycle progression and apoptosis in LNCaP and DU145 cells was examined by flow cytometry and Western blotting. The effect of DBPT on pro-angiogenic molecules was analyzed by Western blotting and by an enzyme-linked immunosorbent assay. RESULTS. DBPT inhibited the growth of LNCaP and DU145 cells with 50% inhibitory concentrations ranging from 1.6 to 5.9 μM. Treating LNCaP and DU145 cells with DBPT led to a time-dependent cell-cycle arrest in the G2/M phase and increased levels of G2/M checkpoint proteins, such as cyclin B1, cdc25C, phosphorylated histone H3, and MPM-2. DBPT induced the phosphorylation of Bcl-xL and Bim, and induced apoptosis, as evidenced by cleavage of caspase and poly (ADP-ribose) polymerase. DBPT also effectively induced apoptosis in Bcl-2-overexpressing DU145 cells. Furthermore, DBPT decreased hypoxia-inducible factor 1α and vascular endothelial growth factor expression in LNCaP cells under both normoxia and hypoxia. CONCLUSIONS. DBPT can suppress proliferation, induce apoptosis, and downregulate pro-angiogenic molecules in prostate cancercells, and might be useful in treating prostate cancer.

Original languageEnglish
Pages (from-to)430-438
Number of pages9
JournalProstate
Volume66
Issue number4
DOIs
Publication statusPublished - Mar 1 2006
Externally publishedYes

Keywords

  • Apoptosis
  • G/M-phase arrest
  • Novel compound
  • Prostate cancer
  • VEGF

ASJC Scopus subject areas

  • Oncology
  • Urology

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