Roasted coffee induction of aldo-keto reductase 1C3 expression in LNCaP human prostate cancer cells is associated with Nrf2 activation
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- Published online on: November 2, 2016 https://doi.org/10.3892/ol.2016.5334
- Pages: 5321-5326
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Abstract
A moderate intake of coffee is associated with a reduced risk of developing certain types of chronic diseases, including many types of cancer. However, the results of epidemiological studies conducted to explore the association between coffee consumption and prostate cancer are inconsistent. Prostate cancer is dependent on androgens for development and growth; therefore the current study analyzed the effect of coffee on the expression of enzymes involved in androgen metabolism in human prostate cancer LNCaP cells. It was observed that a small amount of coffee strongly increased the expression of aldo‑keto reductase 1C3 (AKR1C3), which plays a pivotal role in the synthesis of testosterone and dihydrotestosterone. Treatment with 2.5% (v/v) coffee for 24 h resulted in 5‑fold increase in AKR1C3 gene expression. The active components in coffee were extracted using n‑butanol and it was demonstrated that the major constituents including caffeine, caffeic acid, chlorogenic acid and trigonelline had no effect on AKR1C3 expression even at high concentrations (100 µM). Roasting of coffee beans however enhanced the induction of AKR1C3 gene expression. Activation of nuclear factor‑erythroid‑2‑related factor 2 was observed prior to AKR1C3 induction produced by coffee and this activation was enhanced by roasting the coffee beans. The results of the present study suggest that consumption of roasted coffee may activate androgenic AKR1C3 expression mediated by Nrf2 in human prostate cancer cells and therefore may increase the risk of prostate cancer.