Jeremy Johnson Receives Four-Year Research Grant
Dr. Johnson has received a four year Research Scholar Grant from the American Cancer Society. The Mediterranean diet has long been associated with promoting a healthy lifestyle. Along with the consumption of “good” fats, fruits and vegetables another important factor is the consumption of several Mediterranean herbs including rosemary. This project is examining the phytochemical Carnosol that is naturally found in rosemary, as an agent for inhibiting prostate cancer. This study will seek to understand how Carnosol can target both androgen and estrogen receptors and how it may be used to prevent resistance to commonly used anti-androgen drugs.
The long-term goal is to understand how diterpenes including carnosol simultaneously disrupt AR and ERa for the prevention of prostate cancer. Our central hypothesis is that diterpenes are dual AR and ERa disruptors that promote proteolytic degradation of AR and ERa decreasing the proliferative index of prostate cells. Our hypothesis has been formulated on the basis of our own published data which was the first report of a single chemical entity, carnosol that was able to simultaneously disrupt AR and ERa without agonist properties. Also, the work of several other groups evaluating diterpenes as either AR or ERa antagonists is supportive of our hypothesis.
We plan to test our central hypothesis and accomplish the objective of this proposal by pursuing the following: Aim 1: To characterize the post translational and proteolytic events associated with carnosol induced degradation of AR and ERa in prostate cells. Aim 2: To determine if carnosol interacting with the ligand binding domain is necessary for proteolytic events associated with carnosol induced degradation of ERa in prostate cells. Aim 3: To determine the stage specific chemopreventive efficacy of oral feeding carnosol on prostate cancer initiation and progression using the Nkx3.1/PTEN transgenic prostate cancer mouse model.