Prostate cancer is one of the leading causes of
cancer death in men in Western countries. Epidemiological studies have linked the consumption of fruits and vegetables to a reduced risk of
prostate cancer, and small fruits are particularly rich sources of many active
phytochemical stilbenes, such as
pterostilbene. As a constituent of small fruits such as grapes, berries, and their products,
pterostilbene is under intense investigation as a
cancer chemopreventive agent. Using the p53 wild type LNCaP and p53 null PC3 cells, we found that treatment with
pterostilbene resulted in dose-dependent inhibition of cellular proliferation, which suggested that the interaction of
pterostilbene with the p53 might not fully explain its inhibitory effect on proliferation. In this study, we found that
pterostilbene activated AMPK in both p53 positive and negative human
prostate cancer cells.
Pterostilbene-activated AMPK decreased the activity and/or expression of lipogenic
enzymes, such as
fatty acid synthase (FASN) and
acetyl-CoA carboxylase (ACC). Interestingly, the resolution between apoptosis and growth arrest following AMPK activation is greatly influenced by p53 status. In p53 positive LNCaP cells,
pterostilbene blocked the progression of cell cycle at G1 phase by inducing p53 expression and further up-regulating p21 expression. However,
pterostilbene induced apoptosis in p53 negative PC3 cells. Our results suggest that
pterostilbene may be a functional chemopreventive agent and that dietary exposure to
pterostilbene would be helpful for antiprostate
cancer activity.