Abstract 5369: Effects of resveratrol on chemotherapeutic agent 5-fluorouracil induced DNA damage in prostate and breast cancer cells

Abstract

Abstract Resveratrol is known as a powerful antioxidant present in many foods, especially in grapes and red wine. Recent studies have shown that diets rich in antioxidants, such as Resveratrol, may significantly lower an individual's risk for developing cancer and reduce the chances of metastasis in cancer patients. Previous studies have also shown that cancer patient exposure to 5-fluorouracil (5-FU), a widely used chemotherapeutic agent typically used to treat colon, rectum, head, and neck cancers, causes cell death and apoptosis in cancer cells through various mechanisms, including DNA damage. This study investigated the effects of high concentrations of Resveratrol in human prostate cancer (PC3) cells and human breast cancer (MCF-7) cells exposed to relatively large doses of 5-FU, through the use of the Alkaline Comet Assay. PC3 and MCF-7 cells were exposed to 5-FU at concentrations of 100 µM, 200 µM, 400 µM, and 500 µM for one hour, and then subsequently exposed to Resveratrol at concentrations of 25 µM, 50 µM, and 100 µM for another hour. DNA damage was quantitatively measured using the % DNA in Tail parameter. We found a dose-dependent positive correlation between 5-FU exposure and DNA damage in both cell lines. The addition of Resveratrol in PC3 cells also produced a mean reduction in DNA damage of 45.10% in 25 µM samples, 61.42% in 50 µM samples, and 72.86% in 100 µM samples, in comparison to samples exclusively exposed to 5-FU. Similar trends were also observed in MCF-7 cells, and there was a significant difference between the treated and negative control samples (p < 0.001). In addition, when comparing cell lines, we recorded higher DNA damage values in MCF-7 cells than in PC3 cells when exposed to 5-FU. There was also a greater reduction in DNA damage in PC3 cells than in MCF-7 cells with the addition of Resveratrol in all 5-FU treated samples. These results may possibly indicate higher sensitivity of MCF-7 cells to 5-FU and lower sensitivity to Resveratrol. To further investigate possible underlying mechanisms of Resveratrol in ameliorating DNA damage caused by 5-FU, we performed the Oxygen Radical Absorbance Capacity (ORAC) Assay to determine antioxidant capacity. The antioxidant capacity of various concentrations of resveratrol and 5-FU in conjunction were calculated as Trolox equivalents per liter (TE/L) using individually generated Trolox standard curves. We found that Resveratrol exhibits high antioxidant capacity levels, while 5-FU exhibits limited antioxidant capacity levels. There was a dose-dependent increase of antioxidant capacity measured by the ORAC Assay for both compounds. More research is necessary to further elucidate the mechanisms and pathways involved in DNA repair in cancer cells exposed to high doses of Resveratrol and 5-FU. Citation Format: Michael Xiao, Irene Yeung, Gaju Shrestha, Luis Camberos, Richard A. Robison, Kim L. O'Neill. Effects of resveratrol on chemotherapeutic agent 5-fluorouracil induced DNA damage in prostate and breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5369. doi:10.1158/1538-7445.AM2014-5369