Resveratrol‐induced DNA Damage on MCF‐7 Breast Cancer Cells Through NER Pathway

Abstract

Resveratrol is a (poly)phenol that has been reported to have beneficial properties against several cancers, such as breast cancer (BC). Resveratrol is also known to possess antioxidant capacity and estrogen and antiestrogen‐mimetic activity. BC is a heterogeneous disease in which the behavior and biological characteristics of the tumors can vary; therefore, affecting disease prognosis and treatment selection. Breast tumors can be classified based on three hormonal receptors: estrogen (ER), progesterone (PR), and HER2. Based on their status, four molecular subtypes have been identified: luminal A (ER+, PR+/−, HER2−), luminal B (ER+, PR+/−, HER2+), HER2+ (ER−, PR−, HER2+), and triple‐negative (TN) (ER−, PR−, HER2−).PURPOSESince resveratrol is a (poly)phenol with estrogen mimicking properties and estrogen has been shown to induce DNA damage, the main objective of this study is to assess the DNA damaging and antioxidant potential of resveratrol among the four principal molecular subtypes. Since previous studies from our laboratory show a relationship between ER positivity and DNA repair through the nucleotide excision repair (NER) pathway in BC, we chose to assess DNA damage, through NER pathway, and expression changes in genes related to antioxidant response.METHODSBC cell lines resembling the different molecular subtypes were used to achieve our aim. To assess DNA damaging induction through the NER pathway, the cells were irradiated with ultraviolet C (UVC) light. MCF‐7 (luminal A) cells were cultured and treated with 250 μM resveratrol for 2 hours before and after UVC exposure (20J/m2) and were compared with untreated cells exposed to UVC. After dosing and irradiation DNA damage through the NER pathway was measured using the alkaline comet assay. NFE2L2 expression was measured through RT‐PCR.RESULTSOur results show that both treatments with resveratrol before and after UVC exposure induced DNA damage in MCF‐7 cells. While untreated cells (UVC only) showed a 10.68 ± 3.12%, resveratrol pre‐treated cells had a 29.0 ± 0.88% (p=0.07). MCF‐7 cells treated with resveratrol after UVC exposure had a DNA damage of 65.2 ± 16.57% (p=0.22). Gene expression measurements of NFE2L2 are currently ongoing.CONCLUSIONSAlthough these changes were not statistically significant, they suggest a role of resveratrol in DNA damage induction in MCF‐7 cells upon NER pathway activation. Currently, we are working with the MDA‐MB‐231 (TN), BT‐474 (luminal B), and SK‐BR‐3 (HER2+), to compare the DNA damaging potential of resveratrol among the different molecular BC subtype through the NER pathway. We will also assess protein expression of key NER proteins through western blot.Support or Funding InformationThis study was supported by NIH‐NIGMS #2R25GM096955, #S06GM008239‐20, 9SC1CA182846‐04, #U54CA163068, and G12‐MD007579.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.