Antidiabetic thiazolidinediones induce ductal differentiation but not apoptosis in pancreatic cancer cells

Elisabetta Ceni, Tommaso Mello, Mirko Tarocchi, David W. Crabb, Anna Caldini, Pietro Invernizzi, Calogero Surrenti, Stefano Milani, Andrea Galli

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Aim: Thiazolidinediones (TZD) are a new class of oral antidiabetic drugs that have been shown to inhibit growth of same epithelial cancer cells. Although TZD were found to be ligands for peroxisome proliferator-activated receptor γ (PPARγ), the mechanism by which TZD exert their anticancer effect is presently unclear. In this study, we analyzed the mechanism by which TZD inhibit growth of human pancreatic carcinoma cell lines in order to evaluate the potential therapeutic use of these drugs in pancreatic adenocarcinoma. Methods: The effects of TZD in pancreatic cancer cells were assessed in anchorage-independent growth assay. Expression of PPARγ was measured by reverse-transcription polymerase chain reaction and confirmed by Western blot analysis. PPARγ activity was evaluated by transient reporter gene assay. Flow cytometry and DNA fragmentation assay were used to determine the effect of TZD on cell cycle progression and apoptosis respectively. The effect of TZD on ductal differentiation markers was performed by Western blot. Results: Exposure to TZD inhibited colony formation in a PPARγ-dependent manner. Growth inhibition was linked to G1 phase cell cycle arrest through induction of the ductal differentiation program without any increase of the apoptotic rate. Conclusion: TZD treatment in pancreatic cancer cells has potent inhibitory effects on growth by a PPAR-dependent induction of pacreatic ductal differentiation.

Original languageEnglish (US)
Pages (from-to)1122-1130
Number of pages9
JournalWorld Journal of Gastroenterology
Volume11
Issue number8
StatePublished - Feb 28 2005
Externally publishedYes

Keywords

  • Cancer growth
  • Differentiation
  • Pancreatic cancer
  • PPARγ
  • Thiazolidinediones

ASJC Scopus subject areas

  • Gastroenterology

Fingerprint Dive into the research topics of 'Antidiabetic thiazolidinediones induce ductal differentiation but not apoptosis in pancreatic cancer cells'. Together they form a unique fingerprint.

  • Cite this

    Ceni, E., Mello, T., Tarocchi, M., Crabb, D. W., Caldini, A., Invernizzi, P., Surrenti, C., Milani, S., & Galli, A. (2005). Antidiabetic thiazolidinediones induce ductal differentiation but not apoptosis in pancreatic cancer cells. World Journal of Gastroenterology, 11(8), 1122-1130.