Proteasome inhibition: a new therapeutic strategy to cancer treatment.

Abstract

The ubiquitin-proteasome system is a major pathway for protein degradation. Targeting this pathway using proteasome inhibitors represents a novel approach for the treatment of cancer. Proteasome inhibitors lower cell proliferation and induce apoptosis in solid and hematologic malignancies through multiple mechanisms, including stabilization of cell cycle regulators and pro-apoptotic factors, stimulation of bone morphogenetic protein signaling, inhibition of protein translation, and sensitization to ligand-induced apoptosis. In this connection, proteasome inhibition activates macroautophagy, a compensatory protein degradation system, as well as other pro-survival signaling pathways. Inhibition of these auto-protective responses sensitizes cancer cells to the anti-proliferative effects of proteasome inhibitors.

• Authors: William Ka Kei Wu, Chi Hin Cho, Chung Wa Lee, Kaichun Wu, Daiming Fan, Jun Yu, Joseph Jao Yiu Sung
• Journal: Cancer letters (Cancer Lett) Vol. 293 Issue 1 Pg. 15-22 (Jul 01 2010) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 20133049 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Protease Inhibitors
• Proteasome Inhibitors
• Proteasome Endopeptidase Complex

Topics

• Female
• Humans
• Male
• Neoplasms (drug therapy, enzymology)
• Protease Inhibitors (therapeutic use)
• Proteasome Endopeptidase Complex (metabolism)
• Proteasome Inhibitors