The impact of caffeine on prostate cancer progression : an in vitro study

Abstract

Prostate cancer (PCa) is the most frequent cancer malignancy among men and the third leading cause of cancer death in the developed world. To date, the exact molecular mechanism underlying the role of caffeine one of the major coffee constituents on PCa prognosis is not yet unraveled. Caffeine has many antioxidant, anti-inflammatory and anti carcinogenic properties through the modulation of certain inflammatory markers such as IL-6 and TNF-α. The present study was carried out to evaluate the effect of caffeine on PCa cell lines viability, namely PC3 and PC3-PSMA and assessing as well their inflammatory status by quantifying the gene expression of IL6 and IκB-α. For the viability, WST1 assay was performed and indicated a significant decrease in growth up to 50% with increased caffeine doses depending on the cell type and incubation period (p<0.05). Interestingly, IL-6 concentration increased after 24 hrs incubation with caffeine reaching ELISA levels of 321pg/ml for PC3 cells and 88 pg/ml for PC3-PSMA cells (p<0.05). After 48 hrs IL-6 concentration dropped to 34 pg/ml for PC3 cells and it was undetectable in PC3-PSMA cells. The expression of IL-6 and IκB-α genes were assessed using qRT-PCR. Variation in either caffeine dose or incubation time period had no effect on IκB-α mRNA abundance for both cell lines (p>0.05). High IL-6 expression was found at high caffeine concentration (10 and 20 mM) for PC3 and PC3-PSMA cells (p<0.05). These results demonstrate that caffeine increased inflammation but decreased viability through the stabilization of IκB-α which is perfectly correlated with the levels of NF-κB responsible of cell proliferation and survival.