|Title||Mitochondria-Centric Review of Polyphenol Bioactivity in Cancer Models.|
|Publication Type||Journal Article|
|Year of Publication||2018|
|Authors||Stevens JF, Revel JS, Maier CS|
|Journal||Antioxid Redox Signal|
|Date Published||2018 12 01|
SIGNIFICANCE: Humans are exposed daily to polyphenols in milligram-to-gram amounts through dietary consumption of fruits and vegetables. Polyphenols are also available as components of dietary supplements for improving general health. Although polyphenols are often advertised as antioxidants to explain health benefits, experimental evidence shows that their beneficial cancer preventing and controlling properties are more likely due to stimulation of pro-oxidant and proapoptotic pathways. Recent Advances: The understanding of the biological differences between cancer and normal cell, and especially the role that mitochondria play in carcinogenesis, has greatly advanced in recent years. These advances have resulted in a wealth of new information on polyphenol bioactivity in cell culture and animal models of cancer. Polyphenols appear to target oxidative phosphorylation and regulation of the mitochondrial membrane potential (MMP), glycolysis, pro-oxidant pathways, and antioxidant (adaptive) stress responses with greater selectivity in tumorigenic cells.
CRITICAL ISSUES: The ability of polyphenols to dissipate the MMP (Δψ) by a protonophore mechanism has been known for more than 50 years. However, researchers focus primarily on the downstream molecular effects of Δψ dissipation and mitochondrial uncoupling. We argue that the physicochemical properties of polyphenols are responsible for their anticancer properties by virtue of their protonophoric and pro-oxidant properties rather than their specific effects on downstream molecular targets.
FUTURE DIRECTIONS: Polyphenol-induced dissipation of Δψ is a physicochemical process that cancer cells cannot develop resistance against by gene mutation. Therefore, polyphenols should receive more attention as agents for cotherapy with cancer drugs to gain synergistic activity. Antioxid. Redox Signal.
|Alternate Journal||Antioxid. Redox Signal.|
|PubMed Central ID||PMC6207154|
|Grant List||R01 AT009168 / AT / NCCIH NIH HHS / United States |
S10 RR027878 / RR / NCRR NIH HHS / United States