Medicinal herbs inhibit castrate‐resistant prostate cancer via mechanisms involving AMPK

Abstract

Prostate cancer (PCa) is the second most common type of cancer among males in the USA. Preliminary data has shown that Zyflamend®, a mixture containing extracts of 10 medicinal herbs, inhibited growth of CWR22Rv1 cells (a castrate‐resistant human PCa cell line), by down‐regulating the expression of key mediators of lipogenesis, including SREBP‐1c, fatty acid synthase and HMG CoA reductase. Down‐regulation of lipogenic genes is associated with tumor growth inhibition. These same pathways are negatively regulated by 5’adenosine monophosphate (AMP)‐activated protein kinase (AMPK), a potential tumor suppressor protein that functions as a central energy sensor within the cell. Proliferation of CWR22Rv1 cells was enhanced following chemical inhibition of AMPK by Compound C and inhibited with constitutive over‐expression of AMPK following adenoviral infection. These effects are believed to be mediated by AMPKs phosphorylation of mTOR (mammalian target of rapamycin), a known activator of cell proliferation and a downstream target of AMPK. Similarly, Zyflamend® up‐regulates AMPK activation, inhibits cell growth, and coordinately increases the phosphorylation of down‐stream targets of AMPK, mTOR and acetyl CoA carboxylase (negatively effecting fatty acid synthesis). Thus, our results suggest that the polyherbal mixture Zyflamend® inhibits castrate‐resistant PCa through mechanisms involving AMPK.