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There is agreement that the biological properties of additionally hydroxylated analogs of resveratrol (RVT) may be stronger compared with their parent drug. Here we examined the effect of a novel RVT derivative, 3,3',4,4'-tetrahydroxy-trans-stilbene (3,3',4,4'-THS), on the replicative senescence of human peritoneal mesothelial cells. The study showed that 3,3',4,4'-THS improves the cell proliferative capacity and delays their entry into senescence compared with control and RVT-treated cells. The latter coincided with decreased activity of senescence-associated β-galactosidase and p38 mitogen-activated protein kinase. Besides, 3,3',4,4'-THS preserved functionality of the mitochondria in senescent cells, as evidenced according to increased membrane potential and decreased mitochondrial content. In addition, it induced, to a larger extent than RVT, the production of superoxides and nonspecific reactive oxygen species and intensified their removal. This was probably related to the augmented activity of antioxidative systems, including superoxide dismutase, catalase, and reduced glutathione. The magnitude of DNA injury (8-hydroxy-2'-deoxyguanosine, histone γ-H2A.X) in cells treated with 3,3',4,4'-THS was diminished, which coincided with suppression of the DNA damage response transducer, 53BP1. Altogether, our study shows that 3,3',4,4'-THS is a more efficient antisenescence agent than RVT, which may be associated with its stimulatory effect on reactive oxygen species release, which results in a compensatory induction of antioxidants and concomitant suppression of oxidative DNA injury.

Resveratrol Derivative, 3,3′,4,4′-Tetrahydroxy-trans-Stilbene, Retards Senescence of Mesothelial Cells via Hormetic-Like Prooxidative Mechanism