Physiological Levels of Resveratrol Metabolites are Ineffective as Anti-Leukemia Agents Against Jurkat Leukemia Cells

Abstract

Dietary resveratrol is metabolically transformed in vivo by the intestine and liver to produce resveratrol glucuronides and sulfates in humans. Little is known about the anticancer activities of these metabolic products. The majority of in vitro studies have investigated effects of resveratrol aglycone at supraphysiological levels. Physiological levels of resveratrol-3-O-glucuronide, resveratrol-4′-O-glucuronide, and resveratrol-3-O-sulfate, the major in vivo metabolites of dietary resveratrol, were evaluated as anticancer agents against Jurkat T leukemia cells. Propidium iodide was use to measure cell death and changes in cell cycle, and the mitochondrial membrane dye JC-1 was used to measure changes in mitochondrial membrane potential by flow cytometry. PKH67 was used to evaluate changes in proliferation of the cells by flow cytometry. Jurkat cells were exposed to 0, 2.5, 5, 10, 15, and 20 μM of each resveratrol metabolite, which are concentrations achievable in vivo. None of the resveratrol metabolites were able to kill Jurkat T leukemia cells or alter cell cycle or proliferation at these concentrations. Only resveratrol-3-O-sulfate induced depolarization of mitochondrial membranes but without induction of cell death. These results suggest that the in vivo transformation of resveratrol to these glucuronide and sulfate metabolites renders these agents ineffective against T leukemia cells.