Abstract
Zhang JJ, Wu M, Schoene NW, Cheng WH, Wang TT, Alshatwi AA, Alsaif M, Lei KY. Effect of resveratrol and zinc on intracellular zinc status in normal human prostate epithelial cells. Am J Physiol Cell Physiol 297: C632-C644, 2009. First published June 24, 2009; doi:10.1152/ajpcell.00139.2009.-To evaluate the influence of resveratrol on cellular zinc status, normal human prostate epithelial (NHPrE) cells were treated with resveratrol (0, 0.5, 1, 2.5, 5, and 10 mu M) and zinc [0, 4, 16, and 32 mu M, representing zincdeficient (ZD), zinc-normal (ZN), zinc-adequate (ZA), and zinc-supplemented (ZS) conditions, respectively]. A progressive reduction in cell growth was observed in cells treated with increasing amounts of resveratrol (2.5-10 mu M). Resveratrol at 5 and 10 mu M resulted in a dramatic increase in cellular total zinc concentration, especially in ZS cells. Flow cytometry indicated that 10 mu M resveratrol induced arrest of the cell cycle at the G(2)/M phase in association with the observed cell growth inhibition. Data from an in vitro experiment using zinquin as an indicator of intracellular free Zn(II) status demonstrated complex interactions between resveratrol and Zn(II). Fluorescence spectrofluorometry and fluorescence microscopic analyses revealed that intracellular free labile zinc was progressively elevated from nearly twofold in ZS cells with no resveratrol to multifold in ZA and ZS cells with 10 mu M resveratrol compared with the corresponding ZN cells. Furthermore, increases in cellular zinc status were associated with elevated levels of reactive oxygen species and senescence, as evidenced by morphological and histochemical changes in cells treated with 2.5 or 10 mu M resveratrol, especially in ZA and ZS cells. Taken together, the interaction between resveratrol and zinc in NHPrE cells increases total cellular zinc and intracellular free labile zinc status and, subsequently, reactive oxygen species production and senescence.