Therapeutic potential of flavonoids in cancer: ROS-mediated mechanisms

Cancer is a leading cause of morbidity and mortality around the globe. Reactive oxygen species (ROS) play contradicting roles in cancer incidence and progression. Antioxidants have attracted attention as emerging therapeutic agents. Among these are flavonoids, which are natural polyphenols with established anticancer and antioxidant capacities. Increasing evidence shows that flavonoids can inhibit carcinogenesis via suppressing ROS levels. Surprisingly, flavonoids can also trigger excessive oxidative stress, but this can also induce death of malignant cells. In this review, we explore the inherent characteristics that contribute to the antioxidant capacity of flavonoids, and we dissect the scenarios in which they play the contrasting role as pro-oxidants. Furthermore, we elaborate on the pathways that link flavonoid-mediated modulation of ROS to the prevention and treatment of cancer. Special attention is given to the ROS-mediated anticancer functions that (-)-epigallocatechin gallate (EGCG), hesperetin, naringenin, quercetin, luteolin, and apigenin evoke in various cancers. We also delve into the structure-function relations that make flavonoids potent antioxidants. This review provides a detailed perspective that can be utilized in future experiments or trials that aim at utilizing flavonoids or verifying their efficacy for developing new pharmacologic agents. We support the argument that flavonoids are attractive candidates for cancer therapy.

Automated summary

Cancer is a major cause of global morbidity and mortality. Flavonoids are natural polyphenols with established anticancer and antioxidant capacities. They can inhibit carcinogenesis by suppressing reactive oxygen species (ROS), but also induce cancer cell death through excessive oxidative stress. This review explores the antioxidant capacity and pro-oxidant roles of flavonoids, as well as their pathways in cancer prevention and treatment. The review also emphasizes the anticancer functions of specific flavonoids in various cancers and their structure-function relations.