A Critical Appraisal of the Protective Activity of Polyphenolic Antioxidants against Iatrogenic Effects of Anticancer Chemotherapeutics

Abstract

Polyphenolic compounds, encompassing flavonoids (e.g., quercetin, rutin, and cyanidin) and non-flavonoids (e.g., gallic acid, resveratrol, and curcumin), show several health-related beneficial effects, which include antioxidant, anti-inflammatory, hepatoprotective, antiviral, and anticarcinogenic properties, as well as the prevention of coronary heart diseases. Polyphenols have also been investigated for their counteraction against the adverse effects of common anticancer chemotherapeutics. This review evaluates the outcomes of clinical studies (and related preclinical data) over the last ten years, with a focus on the use of polyphenols in chemotherapy as auxiliary agents acting against oxidative stress toxicity induced by antitumor drugs. While further clinical studies are needed to establish adequate doses and optimal delivery systems, the improvement in polyphenols’ metabolic stability and bioavailability, through the implementation of nanotechnologies that are currently being investigated, could improve therapeutic applications of their pharmaceutical or nutraceutical preparations in tumor chemotherapy.

Harnessing the Power of Polyphenols: A New Frontier in Disease Prevention and Therapy

“…Epidemiological research indicates that cancer pathologies are linked to urban lifestyles, dietary habits, and environmental factors [ 42 , 43 ]. Individuals are prone to experience a variety of harmful side effects connected with present cancer therapies such as chemotherapy, radiotherapy, and immunotherapy [ 44 ].…”

“…The natural world has often served as a reservoir for novel bioactive compounds in the pursuit of effective chemotherapy agents, with plant polyphenols emerging as the most recognized beneficial dietary constituents. Owing to their structurally diverse nature, they manifest a broad spectrum of biological properties [ 43 ]. Evidence from various observational, experimental, and clinical inquiries has highlighted a significant relationship between regular polyphenol consumption and a reduced cancer risk [ 43 ].…”

“…Owing to their structurally diverse nature, they manifest a broad spectrum of biological properties [ 43 ]. Evidence from various observational, experimental, and clinical inquiries has highlighted a significant relationship between regular polyphenol consumption and a reduced cancer risk [ 43 ]. Through the modulation of multiple cellular signaling pathways via interactions with various target proteins, polyphenols can elicit their anticancer effects [ 45 ].…”

“…These substances can influence the processes of carcinogenesis through diverse mechanisms [ 46 ]. Polyphenols feature anti-inflammatory, antiproliferative, anti-angiogenic, autophagic, and apoptotic functions [ 43 , 44 , 47 ]. They are able to aim for numerous cellular processes, such as gene expression, cell cycle proliferation, cellular migration, and progression, to demonstrate their anticancer effects.…”

“…By modulating important signaling pathways (PI3K/Akt, EGFR/MAPK, NF-κB) ( Figure 2 ), polyphenols can (i) neutralize reactive oxygen species (ROS) and other free radicals; (ii) reduce DNA mutations and damage; (iii) inhibit the cell cycle; (iv) induce apoptosis; and (v) downregulate cell proliferation. Furthermore, polyphenols may exert anticancer effects through various pathways, such as the cell death receptor pathway, mitochondria-mediated apoptosis via ROS generation, and the perforin-granzyme apoptotic route [ 43 , 49 ]. Moreover, phenolic substances can decrease tumor expression through the p53 pathway while also regulating metabolism and cell formation ( Figure 2 ).…”