Keynote Lecture “Resveratrol and its analogues – shall we always correct nature?”

Resveratrol (trans-3,4′,5-trihydroxystilbene), a naturally occurring hydroxystilbene, is considered an essential antioxidative constituent of red wine and many medicinal plants. Moreover, resveratrol, its metabolite piceatannol, and higher hydroxylated analogues were reported to have cytotoxic activities. As a key factor for their activity, the hydroxyl groups are considered [1]. Therefore, one can wonder whether structures with more hydroxyl groups will have a more potent antioxidant and cytotoxic effect. Moreover, is there a link between antioxidant and cytotoxic activity? We have synthesized several other polyhydroxylated resveratrol analogues and studied their pro-/antioxidant and cytotoxicity properties to answer this question. Our experiments suggested that not only the number of hydroxyl groups and their disposition in aromatic rings play an important role. Our experiments started from the mitochondrial model and showed that oxidation of ortho-hydroxystilbenes (e.g., piceatannol) results in cytotoxic ortho-semiquinones production. Further investigations revealed that these intermediates undergo redox-cycling, consuming additional oxygen and forming cytotoxic oxygen radicals. In contrast, compounds without such substitution patterns, (e.g., resveratrol) did not show such activity [2]. Following this path, we have performed several in vitro studies employing different cancer cell models showing different cytotoxic effects exerted by resveratrol and analogues [3], [4]. In this talk, our results will be confronted with findings from other groups. The results of our investigation suggest that resveratrol has an optimal structure combining antioxidant and cytostatic properties. A further increase in the number of hydroxyl groups may result in pro-oxidative activity that is harmful to cells.

Publikationsverlauf

Artikel online veröffentlicht:
12. Dezember 2022

• References

• 1 Pecyna P, Wargula J, Murias M. et al. More Than Resveratrol: New Insights into Stilbene-Based Compounds. Biomolecules 2020; 10
• 2 Murias M, Jäger W, Handler N. et al. Antioxidant, prooxidant and cytotoxic activity of hydroxylated resveratrol analogues: structure-activity relationship. Biochem Pharmacol 2005; 69: 903-912
• 3 Murias M, Luczak MW, Niepsuj A. et al. Cytotoxic activity of 3,3′,4,4′,5,5′-hexahydroxystilbene against breast cancer cells is mediated by induction of p 53 and downregulation of mitochondrial superoxide dismutase. Toxicol In Vitro 2008; 22: 1361-1370
• 4 Kucinska M, Piotrowska H, Luczak MW. et al. Effects of hydroxylated resveratrol analogs on oxidative stress and cancer cells death in human acute T cell leukemia cell line: prooxidative potential of hydroxylated resveratrol analogs. Chem Biol Interact 2014; 209: 96-110