Title:Selected Attributes of Polyphenols in Targeting Oxidative Stress in Cancer
Volume: 15
Issue: 5
Author(s): Visnja Stepanic, Ana Cipak Gasparovic, Koraljka Gall Troselj, Dragan Amic and Neven Zarkovic
Affiliation:
Keywords:
Adjuvant, Anticancer therapy, Antioxidative, Curcumin, EGCG, Flavonoids, NRF2, Polyphenols, Pro-oxidative.
Abstract: Various plant polyphenols have been recognized as redox active molecules. This review discusses
some aspects of polyphenols’ modes of redox action, corresponding structure-activity relationships
and their potential to be applied as adjuvants to conventional cytostatic drugs. Polyphenols’ antioxidative
capacity has been discussed as the basis for targeting oxidative stress and, consequently, for their chemopreventive
and anti-inflammatory activities, which may alleviate side-effects on normal cells arising from
oxidative stress caused by cytostatics. Some polyphenols may scavenge various free radicals directly, and
some of them are found to suppress free radical production through inhibiting NADPH oxidases and xanthine
oxidase. Additionally, polyphenols may increase antioxidative defense in normal cells by increasing the activity of
NRF2, transcription factor for many protective proteins. The activation of the NRF2-mediated signaling pathways in cancer
cells results in chemoresistance. Luteolin, apigenin and chrysin reduce NRF2 expression and increase the chemosensitivity
of cancer cells to cytostatic drugs. Their common 5,7-dihydroxy-4H-chromen-4-one moiety, may represent a starting
pharmacophore model for designing novel, non-toxic compounds for overcoming chemoresistance. However, prooxidative
activity of some polyphenols (quercetin, EGCG) may also provide a basis for their use as chemotherapeutic adjuvants
since they may enhance cytotoxic effects of cytostatics selectively on cancer cells. However, considerable caution
is needed in applying polyphenols to anticancer therapy, since their effects greatly depend on the applied dose, the cell
type, exposure time and environmental conditions.
