Targeting ubiquitin-proteasome pathway by natural, in particular polyphenols, anticancer agents: Lessons learned from clinical trials

• Published in: Cancer letters 2018-10, Vol.434, p.101-113
• Main Authors: Nabavi, Seyed Fazel, Atanasov, Atanas G., Khan, Haroon, Barreca, Davide, Trombetta, Domenico, Testai, Lara, Sureda, Antoni, Tejada, Silvia, Vacca, Rosa Anna, Pittalà, Valeria, Gulei, Diana, Berindan-Neagoe, Ioana, Shirooie, Samira, Nabavi, Seyed Mohammad
• Format: Article
• Language: English
• Subjects: Amino acids; Anti-cancer agents; Antitumor agents; Apoptosis; Bladder cancer; Breast cancer; Cancer; Cancer therapies; Cell cycle; Chemotherapy; Clinical trials; Colorectal cancer; Drug development; Enzymatic modulator; Enzymes; Fibroblasts; Homeostasis; Kinases; Metabolic networks; Metastasis; Oncoproteins; Pancreatic cancer; Polyphenols; Prostate cancer; Proteasome; Proteasomes; Proteins; Proteolysis; Regulatory proteins; Therapeutic applications; Tumors; Ubiquitin; Ubiquitin-proteasome pathway
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2018.07.018

The ubiquitin-proteasome pathway (UPP) is the main non-lysosomal proteolytic system responsible for degradation of most intracellular proteins, specifically damaged and regulatory proteins. The UPP is implicated in all aspects of the cellular metabolic networks including physiological or pathological conditions. Alterations in the components of the UPP can lead to stabilization of oncoproteins or augmented degradation of tumour suppressor favouring cancer appearance and progression. Polyphenols are natural compounds that can modulate proteasome activity or the expression of proteasome subunits. All together and due to the pleiotropic functions of UPP, there is a great interest in this proteasome system as a promising therapeutic target for the development of novel anti-cancer drugs. In the present review, the main features of the UPP and its implication in cancer development and progression are described, highlighting the importance of bioactive polyphenols that target the UPP as potential anti-cancer agents. •The ubiquitin-proteasome pathway is the main non-lysosomal proteolytic system.•Changes in ubiquitin-proteasome pathway components can alter stability of oncoproteins.•Changes in the pathway may increase degradation of tumour suppressor components, favouring cancer appearance and progression.•Polyphenols are natural compounds capable of modulating proteasome activity and/or the expression of proteasome subunits.•Its pleiotropic functions make it a promising therapeutic target for the development of novel anti-cancer drugs.