Pro-Oxidant Effect of Resveratrol on Human Breast Cancer MCF-7 Cells is Associated with CK2 Inhibition

Abstract

Casein kinase 2 (CK2) plays a critical role in the proliferation and apoptosis of cancer cells. Resveratrol is a bioactive compound with anticancer and anti-inflammatory effects. This study investigated the pro-oxidant cytotoxic effects of resveratrol in association with the inhibition of CK2 activity on human breast carcinoma cells MCF-7. We showed that resveratrol and TBB, an inhibitor of CK2, decreased cell viability in a concentration dependent manner with an IC₅₀ value of 238 µM and 106 µM after 24 h, of treatment, respectively. Resveratrol and TBB decreased CK2 activity by 1.6 and 1.4-fold, respectively, and both significantly decreased mitochondrial membrane potential. However, only resveratrol increased reactive oxygen species (ROS) levels by 1.7-fold as opposed to TBB, which did not affect ROS levels. Indeed, incubating MCF-7 cells with the antioxidant polyethylene glycol-catalase (PEG-CAT) preserved cell viability from the cytotoxic effects of resveratrol, but not from TBB toxicity. This effect seemed to be related to PEG-CAT ability to prevent CK2 inhibition induced by resveratrol incubation. In conclusion, this study demonstrated that the cytotoxic effect of resveratrol on MCF-7 cells might be associated with its pro-oxidant action, which inhibited CK2 activity, affecting cell viability and mitochondrial function.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ Contributions

PSC, TE-B, JLS and EF conceived and designed the study. PSC, PSR and CF performed the experiments. PSC, CF, TE-B and EF analyzed the data. PSC, CF, TE-B, JSL and EF wrote the manuscript. All authors read and approved the final manuscript.

Availability of Data and Materials

All data generated or analyzed in this study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, 001) and Fundação do Câncer. The funders had no role in the study design, in the data collection and analysis, in the decision to publish or in manuscript preparation.