Resveratrol-3-O-glucuronide and resveratrol-4’-O-glucuronide reduce DNA strand breakage but not apoptosis in Jurkat T cells treated with camptothecin

Authors: Zunino, Susan; Storms, David

Submitted to: Oncology Letters
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/1/2017
Publication Date: 5/19/2017
Citation: Zunino, S.J., Storms, D.H. 2017. Resveratrol-3-O-glucuronide and resveratrol-4’-O-glucuronide reduce DNA strand breakage but not apoptosis in Jurkat T cells treated with camptothecin. Oncology Letters. 14:2517-2522.

Interpretive Summary: Resveratrol is found in grapes, peanuts, wine, and blueberries and has received a great deal of attention as an antioxidant and for its potential health benefits. When resveratrol is consumed, the intestine and liver change resveratrol by adding sugar and sulfur groups to the resveratrol molecule. These new molecules are called metabolites and they circulate in the body. Not much is known about these metabolites. We determined if some of these metabolites could decrease DNA damage. DNA damage is often one of the causes of cancer. We used a T cell line as a model to test whether or not the addition of these sugar or sulfur groups could reduce damage to DNA. We treated these cells with resveratrol metabolites and measured the amount of DNA damage after incubating the cells with two chemotherapeutic drugs, camptothecin and topotecan. DNA damage was measured using special fluorescent dyes and a laser-activated fluorescence detector. The results showed that two of the resveratrol metabolites were able to partially protect the DNA in the cells from breaking. The cells still died but the two metabolites with sugars attached were able to significantly reduce the number of DNA breaks per cell. These results suggest that some metabolites of resveratrol found in the body are able to protect cells from DNA damage. This is an important finding since there are many environmental agents that humans are exposed to every day and adding foods with resveratrol or other antioxidants may protect our DNA from damage.

Technical Abstract: Resveratrol has been reported to inhibit or induce DNA damage depending upon the type of cell and experimental conditions. Dietary resveratrol is present in the body mostly as metabolites and little is known about the activities of these metabolic products. We evaluated physiologically obtainable levels of resveratrol-3-O-glucuronide, resveratrol-4’-O-glucuronide, and resveratrol-3-O-sulfate for their ability to protect Jurkate T cells against DNA damage induced by two topoisomerase I inhibitors camptothecin and topotecan. The cells were either pretreated for 24 h with the 10 microM or each metabolite prior to DNA damage or co-treated with metabolites and drugs. Histone 2AX phosphorylation and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were used to determine DNA damage and apoptosis was measured using an antibody against cleaved poly ADP-ribose polymerase. Cells were evaluated by flow cytometry. We found that pretreatment of cells with resveratrol-3-O-glucuronide and resveratrol-4’-O-glucuronide reduced the mean fluorescent intensity of staining for DNA strand breaks after treatment with camptothecin but did not alter the percent of cells undergoing apoptosis. These results suggest that the resveratrol glucuronides partially protected the cells from DNA damage and may have benefit for maintaining health.