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Drug Resist Updat. 1999 Aug;2(4):215-223.

Proteasome inhibitors as potential novel anticancer agents.

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Drug Discovery Program, H. Lee Moffitt Cancer Center & Research Institute, Department of Biochemistry and Molecular Biology, College of Medicine, University of South Florida, Tampa, FL, 33612, USA


Ubiquitin/proteasome-dependent proteolysis plays an essential role in degrading regulatory proteins and thereby controlling processes of cell proliferation and cell death (apoptosis). Most recent experiments using cell cultures and mouse models have demonstrated that proteasome inhibitors induce cancer cell apoptosis and therefore inhibit tumor growth. The proteasome inhibitors have the following unique features: (i) greater apoptosis-inducing potency when tested in various human tumor cell lines than current anticancer drugs; (ii) ability to selectively target transformed and tumor, but not normal, human cells; and (iii) ability to overcome tumor cell resistance to cytotoxic therapies. We suggest that proteasome inhibitors have potential use as novel anticancer agents.


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