In the current study, we assess the chemosensitization activity of the naturally occurring polyphenols resveratrol (RES) and pterostilbene (PTER) to 5-Fluorouracil (5-FU) in Burkitt’s B-cell lymphoma. RES is a stilbenoid compound found in a variety of fruits, plants, and nuts. In addition to antioxidant and anti-aging properties, RES has been shown to exhibit significant anti-tumor activity against a variety of malignancies. Since the compound is typically protective of normal cells, its anti-cancer activity makes it a promising candidate as both a chemopreventative nutritional supplement and a chemotherapeutic agent. PTER, an analog of RES, has likewise shown anti-cancer activity. Its therapeutic potential, however, is much less understood. Recent studies have investigated the use of these and other natural compounds in adjuvant chemotherapy strategies, many of which continue to produce underwhelming rates of response. Here, we investigate the chemosensitization capacity of both RES and PTER to 5-FU, a commonly used drug in chemotherapy, in healthy lymphocytes and in Burkitt’s B-cell lymphoma (Raji) cells. MTS assays are used to measure the viability of malignant and normal lymphocytes after 5-FU treatment with or without co-incubation of RES, PTER, or RES/PTER combinations. We find that Raji co-incubation with physiologically relevant concentrations (<10uM) of either RES or PTER significantly increases 5-FU toxicity in Raji cells, with data suggesting PTER to be slightly more effective than RES. Interestingly, RES/PTER combinatorial treatments further increase chemosensitization, an important finding considering the typically low bioavailability of each individual compound in vivo. Together, these data support the potential use of RES as a chemosensitizing adjuvant and provide new evidence that its analog, PTER, also possesses significant chemosensitization capacity. Furthermore, our studies suggest that low physiological concentrations of PTER and RES may be still be sufficient to induce significant anti-cancer effects.

Citation Format: Connor J. Peck, Michelle H. Townsend, Kim L. O'Neill. Resveratrol and pterostibene selectively chemosensitize Burkitt’s lymphoma cells to 5-Fluorouracil [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 252. doi:10.1158/1538-7445.AM2017-252