Resveratrol Modulates the Redox-status and Cytotoxicity of Anticancer Drugs by Sensitizing Leukemic Lymphocytes and Protecting Normal Lymphocytes

Anticancer Res. 2019 Jul;39(7):3745-3755. doi: 10.21873/anticanres.13523.

Abstract

Background/aim: The study is directed to the effect of resveratrol on the redox-status and viability of leukemic and normal lymphocytes, as well as its ability to sensitize leukemic lymphocytes to anticancer drugs.

Materials and methods: Cytotoxicity was analyzed by trypan blue staining, apoptosis - by Annexin V test, and oxidative stress - by the intracellular levels of reactive oxygen species (ROS) and protein-carbonyl products.

Results: Incubation of resveratrol in combination with the majority of anticancer drugs resulted in higher toxicity than resveratrol or drug alone. In the case of leukemic lymphocytes treated with barasertib and everolimus in the presence of resveratrol, synergistic cytotoxicity was accompanied by strong induction of apoptosis, increased levels of hydroperoxides and insignificant changes in protein-carbonyl products. None of these parameters changed in normal lymphocytes.

Conclusion: Resveratrol is a promising supplementary compound for anticancer therapy, that may allow reduction of the therapeutic doses of barasertib and everolimus, minimizing their side-effects.

Keywords: Cancer; apoptosis; chemotherapy; oxidative stress; resveratrol.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Humans
  • Leukemia / drug therapy
  • Leukemia / metabolism*
  • Lymphocytes / drug effects*
  • Lymphocytes / metabolism
  • Oxidation-Reduction
  • Protective Agents / pharmacology*
  • Reactive Oxygen Species / metabolism*
  • Resveratrol / pharmacology*

Substances

  • Antineoplastic Agents
  • Protective Agents
  • Reactive Oxygen Species
  • Resveratrol