The role of polyphenols in overcoming cancer drug resistance: a comprehensive review

Abstract

Chemotherapeutic drugs are used to treat advanced stages of cancer or following surgery. However, cancers often develop resistance against drugs, leading to failure of treatment and recurrence of the disease. Polyphenols are a family of organic compounds with more than 10,000 members which have a three-membered flavan ring system in common. These natural compounds are known for their beneficial properties, such as free radical scavenging, decreasing oxidative stress, and modulating inflammation. Herein, we discuss the role of polyphenols (mainly curcumin, resveratrol, and epigallocatechin gallate [EGCG]) in different aspects of cancer drug resistance. Increasing drug uptake by tumor cells, decreasing drug metabolism by enzymes (e.g. cytochromes and glutathione-S-transferases), and reducing drug efflux are some of the mechanisms by which polyphenols increase the sensitivity of cancer cells to chemotherapeutic agents. Polyphenols also affect other targets for overcoming chemoresistance in cancer cells, including cell death (i.e. autophagy and apoptosis), EMT, ROS, DNA repair processes, cancer stem cells, and epigenetics (e.g. miRNAs).

Understanding the Prooxidant Action of Plant Polyphenols in the Cellular Microenvironment of Malignant Cells: Role of Copper and Therapeutic Implications

“…Most plant derived polyphenols possess both antioxidant as well as prooxidant properties ( George et al, 2011 ; Asuzu et al, 2019 ; Jomová et al, 2019 ; Maleki Dana et al, 2022 ). Several studies have shown that in the presence of copper ions polyphenolic compounds can act as pro oxidants leading to cellular breakage of DNA via ROS formation ( Said Ahmad et al, 1992 ; Ahsan and Hadi, 1998 ; Khan and Hadi, 1998 ; Ahmad et al, 2000 ; Azam et al, 2004 ; Ahmad et al, 2005 ; Farhan et al, 2015a ; Arif et al, 2015 ).…”

Natural Products in Preventing Tumor Drug Resistance and Related Signaling Pathways

“…At present, chemotherapy remains the main treatment for tumors [ 35 ]. Mutations of the targets of chemotherapeutic drugs, or modifications of the signaling pathway components involved, can reduce drug efficacy so that the tumor develops resistance to the chemotherapeutic drugs [ 36 ]. The mechanisms of tumor resistance to chemotherapeutic drugs are still very complex [ 37 ].…”

Chemosensitization of U-87 MG Glioblastoma Cells by Neobavaisoflavone towards Doxorubicin and Etoposide

“…Due to ineffective therapy, there is an urgent need to develop a novel regimen that would be able to overcome such obstacles as GB tumor heterogeneity or drug resistance. One of the therapeutical strategies that are being taken into consideration is a combined treatment targeting multiple pathways crucial for neoplastic cell survival [ 18 , 19 ]. This is the basis of the process called chemosensitization, which assumes the use of a non-toxic compound that is able to enhance the activity of a chemotherapeutic [ 27 , 36 ].…”

“…A combined therapy involving a chemical that targets one of the mechanisms of chemoresistance, including drug uptake, its metabolism, or cell death and survival, is expected to improve pharmacotherapy efficacy. The compounds that possess such properties are polyphenols [ 19 ].…”