In the past 15 years, the
proteasome has been validated as an anti-
cancer drug target and
20S proteasome inhibitors (such as
bortezomib and
carfilzomib) have been approved by the FDA for the treatment of
multiple myeloma and some other liquid
tumors. However, there are shortcomings of clinical
proteasome inhibitors, including severe
toxicity, drug resistance, and no effect in solid
tumors. At the same time, extensive research has been conducted in the areas of natural compounds and old drug repositioning towards the goal of discovering effective, economical, low toxicity
proteasome-inhibitory anti-
cancer drugs. A variety of dietary
polyphenols, medicinal molecules, metallic complexes, and
metal-binding compounds have been found to be able to selectively inhibit
tumor cellular proteasomes and induce apoptotic cell death in vitro and in vivo, supporting the clinical success of specific
20S proteasome inhibitors
bortezomib and
carfilzomib. Therefore, the discovery of natural
proteasome inhibitors and researching old drugs with
proteasome-inhibitory properties may provide an alternative strategy for improving the current status of
cancer treatment and even prevention.