Inhibition of the ubiquitin-proteasome system by natural products for cancer therapy.
The ubiquitin-proteasome system plays a critical role in selective protein degradation and regulates almost all cellular events such as cell cycle progression, signal transduction, cell death, immune responses, metabolism, protein quality control, development, and neuronal function. The recent approval of bortezomib, a synthetic proteasome inhibitor, for the treatment of relapsed multiple myeloma has opened the way to the discovery of drugs targeting the proteasome and ubiquitinating and deubiquitinating enzymes as well as the delivery system. To date, various synthetic and natural products have been reported to inhibit the components of the ubiquitin-proteasome system. Here, we review natural products targeting the ubiquitin-proteasome system as well as synthetic compounds with potent inhibitory effects.
Tsukamoto
Sachiko
S
Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan. sachiko@kumamoto-u.ac.jp
Yokosawa
Hideyoshi
H
D000447:Aldehydes / Q000737:chemistry / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001897:Boronic Acids / Q000737:chemistry / Q000494:pharmacology; D007659:Ketones / Q000737:chemistry / Q000494:pharmacology; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects* / Q000378:metabolism; D061988:Proteasome Inhibitors; D025801:Ubiquitin / Q000378:metabolism*
D000447:Aldehydes; D000972:Antineoplastic Agents, Phytogenic; D001897:Boronic Acids; D007659:Ketones; D007783:Lactones; D010456:Peptides, Cyclic; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex