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Cancer Lett. 2018 Oct 10;434:101-113. doi: 10.1016/j.canlet.2018.07.018. Epub 2018 Jul 17.

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

Author information

1
Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
2
The Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Postępu 36A, Jastrzębiec, 05-552, Magdalenka, Poland; Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, A-1090, Vienna, Austria.
3
Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakistan.
4
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98168, Messina, Italy. Electronic address: dbarreca@unime.it.
5
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98168, Messina, Italy.
6
Department of Pharmacy, University of Pisa, Pisa, Italy; Interdepartmental Center of Nutrafood, University of Pisa, Pisa, Italy.
7
Research Group on Community Nutrition and Oxidative Stress (NUCOX) and CIBEROBN (Physiopathology of Obesity and Nutrition CB12/03/30038), University of Balearic Islands, Palma de Mallorca, E-07122, Balearic Islands, Spain.
8
Laboratory of Neurophysiology, Department of Biology, University of Balearic Islands, Ctra. Valldemossa, Km 7,5, Ed, Guillem Colom, 07122, Balearic Islands, Spain.
9
Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, Italian National Council of Research, Bari, Italy.
10
Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.
11
MEDFUTURE-Research Center for Advanced Medicine, "Iuliu-Hatieganu" University of Medicine and Pharmacy, Marinescu 23 Street, 400337, Cluj-Napoca, Romania.
12
MEDFUTURE-Research Center for Advanced Medicine, "Iuliu-Hatieganu" University of Medicine and Pharmacy, Marinescu 23 Street, 400337, Cluj-Napoca, Romania; Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 23 Marinescu Street, 400337, Cluj-Napoca, Romania; Department of Functional Genomics and Experimental Pathology, The Oncology Institute "Prof. Dr. Ion Chiricuta", Republicii 34 Street, 400015, Cluj-Napoca, Romania.
13
Department of Pharmacology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
14
Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. Electronic address: nabavi208@gmail.com.

Abstract

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.

KEYWORDS:

Anti-cancer agents; Cancer; Enzymatic modulator; Oncoproteins; Polyphenols; Proteasome; Ubiquitin; Ubiquitin-proteasome pathway

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