The proteasome inhibitor MG132 induces apoptosis in human pancreatic cancer cells

Moritz N. Wente, Guido Eibl, Howard A. Reber, Helmut Friess, Markus W. Büchler, Oscar J. Hines

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The ubiquitin-proteasome system plays a critical role in the regulation of programmed cell death. Proteasome inhibitors induce apoptosis in various cancer cells and have antitumor effects in murine tumor models. In the present study, we investigated whether the cell-permeable proteasome inhibitor MG132 (carbobenzoxyl-L-leucyl-L-leucyl-L-leucinal) reduced the growth of a human pancreatic cancer cell line through induction of apoptosis in vitro. The effects of MG132 (0.125- 1.000 μM) on the growth of the human pancreatic cancer cell line BxPC-3 were analyzed by cell count and MTT assay. Apoptosis was determined by FACS analysis after annexin V and propidium iodide staining and the enrichment of intracellular nucleosomes. The proteasome inhibitor MG132 decreased cell growth of the human pancreatic cancer cell line BxPC-3 in a dose- and time-dependent manner. This effect was at least in part mediated by the induction of apoptosis. A combination therapy with standard cytotoxic agents and proteasome inhibitors could potentially be a novel therapeutic strategy in treatment of pancreatic cancer.

Original languageEnglish
Pages (from-to)1635-1638
Number of pages4
JournalOncology Reports
Volume14
Issue number6
DOIs
StatePublished - Dec 2005
Externally publishedYes

Keywords

  • Apoptosis
  • Pancreatic cancer
  • Proteasome inhibition

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