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This Article Full Text Full Text (PDF) All Versions of this Article: 297/3/C632    most recent 00139.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Zhang, J. J. Articles by Lei, K. Y. PubMed PubMed Citation Articles by Zhang, J. J. Articles by Lei, K. Y.

CELLULAR AND MITOCHONDRIAL METABOLISM

Effect of resveratrol and zinc on intracellular zinc status in normal human prostate epithelial cells

¹Department of Nutrition and Food Science, University of Maryland, College Park; ²Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, US Department of Agriculture, Beltsville, Maryland; and ³Department of Food Science and Nutrition and ⁴Center of Excellence for Biotechnology Research, King Saud University, Riyadh, Saudi Arabia/

Submitted 27 March 2009 ; accepted in final form 16 June 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 µM) and zinc [0, 4, 16, and 32 µM, representing zinc-deficient (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 µM). Resveratrol at 5 and 10 µM resulted in a dramatic increase in cellular total zinc concentration, especially in ZS cells. Flow cytometry indicated that 10 µM resveratrol induced arrest of the cell cycle at the G₂/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 µM 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 µM 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.

nutrient interaction; zinquin