| Over the last several decades epidemiological, human migratory studies, pre-clinical and even early phase clinical trials have suggested that dietary constituents may offer a protective effect in reducing the incidence of multiple cancers, including cancer of the prostate. Given the potential that some of these compounds have shown in pre-clinical and even some clinical investigations, it is essential to further identify and develop promising new agents in the hope of creating a broad spectrum of cancer chemopreventive agents. In our studies, we characterized two agents for prostate cancer chemoprevention: carnosol and alpha-mangostin. Carnosol, a dietary diterpene, found in Mediterranean herbs including basil, oregano, sage, and thyme has been shown to decrease prostate cancer cell viability. In our analysis we found carnosol to function as a dual disruptor of the androgen and estrogen receptor-alpha using in vitro and in vivo models. Further study found these traits to be unique when compared to FDA approved anti-androgens and anti-estrogens. alpha-Mangostin, a dietary xanthone, isolated from the mangosteen fruit, was also observed to decrease prostate cancer cell viability. We evaluated alpha-mangostin for kinase inhibition against 50 different kinases. Of those, alpha-mangostin was found to be most effective against CDK4. Our analysis describes the in vitro and in vivo inhibition of prostate cancer using alpha-mangostin. We are proposing that alpha-mangostin and carnosol have unique mechanisms of action and may be further developed as cancer chemopreventive agents. |
