The proteasome inhibitor MG132 induces apoptosis in human pancreatic cancer cells.
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 microM) 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.
Wente
Moritz N
MN
Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany.
Eibl
Guido
G
Reber
Howard A
HA
Friess
Helmut
H
Büchler
Markus W
MW
Hines
Oscar J
OJ
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology*; D009707:Nucleosomes / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D009707:Nucleosomes; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde