Advances in Protein and Peptide Sciences

Advances in Protein and Peptide Sciences

Indexed in: EBSCO, Ulrich's Periodicals Directory

Advances in Protein and Peptide Sciences is a book series focused on leading-edge research on the structure, physical properties, and functions of proteins and peptides. The series presents highly ...
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Natural Proteasome Inhibitors for Battling Cancer

Pp. 272-308 (37)

Huanjie Yang, Kristin R. Landis-Piwowar, Di Chen, Vesna Milacic and Q. Ping Dou

Abstract

The proteasome is a multicatalytic protease complex that degrades most endogenous proteins including misfolded or damaged proteins to ensure normal cellular function. The ubiquitin-proteasome degradation pathway plays an essential role in multiple cellular processes, including cell cycle progression, proliferation, apoptosis and angiogenesis. It has been shown that human cancer cells are more sensitive to proteasome inhibition than normal cells, indicating that a proteasome inhibitor could be used as a novel anticancer drug. Indeed, this idea has been supported by the encouraging results of the clinical trials using the proteasome inhibitor Bortezomib (Velcade, PS-341), a drug approved by the US Food and Drug Administration (FDA). Though successful in improving clinical outcomes when Bortezomib was used in hematological malignancies, relapse often occurs in those patients who responded initially. Recently, several second-generation of proteasome inhibitors (including carfilzomib, marizomib, and MLN9708) have been applied in clinics. Furthermore, several natural compounds, including the microbial metabolite lactacystin, green tea polyphenols, and traditional medicinal triterpenes, have been shown to be potent proteasome inhibitors. These findings suggest the potential use of natural proteasome inhibitors as not only chemopreventive and chemotherapeutic agents, but also tumorsensitizers to conventional radiotherapy and chemotherapy. In this eBook chapter, we will summarize the structure and biological activities of the proteasome and several natural compounds with proteasome-inhibitory activity, and will discuss the potential use of these compounds for the prevention and treatment of human cancers.

Keywords:

Ubiqutin, proteasome, ptoteasomal chymotrypsin-like activity, cell cycle arrest, apoptosis, proteasome inhibitor, nucleophilic suceptibility, bortezomib, natural products, β-lactone, tea polyphenols, isoflavonoids, triterpenes, anti-proliferation, anti-tumor, cancer prevention, cancer treatment, clinical trials, chemosensitization, drug resistance.

Affiliation:

Barbara Ann Karmanos Cancer Institute, and the Department of Oncology School of Medicine, Wayne State University, 540.1 HWCRC, 4100 John R. Road, Detroit, Michigan 48201, USA.