A Healthier Wisconsin

A Novel Metabolism of Microsomal Epoxide Hydrolase and Prostate Cancer

Investigating the metabolism of microsomal expoxide hydrolase (mEH) to identify potential paths toward new therapeutic treatments for prostate cancer

Full Project Name:A Novel Metabolism of Microsomal Epoxide Hydrolase and Prostate CancerPrincipal Investigator:Kasem Nithipatikom, PhD, Pharmacology and ToxicologyCo-Investigator:Carol L. Williams, PhD, Pharmacology and ToxicologyAward Amount:$150,000
Award Date
Project Duration:24 months

Project Description Narrative:

Prostate cancer is the most diagnosed cancer and the second leading cause of cancer death among men in the United States. Risk of prostate cancer development is associated with age, family history, race, diet, and other factors, with the risk being greater in men who are over age 50 and African-American. The majority of mortality from prostate cancer is a result of tumor spread beyond the prostate and/or tumor progression to hormone refractory.

The process of metastasis is a complex multi-stage process that includes growth, vascularization, adhesion, extravasation, and invasion. Therefore, a discovery of new molecular targets that can inhibit cell proliferation and invasion is among the most important endeavors in prostate cancer therapy. Through this award, a collaborative team aims to investigate the new metabolism of microsomal expoxide hydrolase (mEH) in the regulation of prostate carcinoma cell proliferation and invasion in order to identify potential paths toward new therapeutic treatments for prostate cancer.

Collaborator: Bruce D. Hammock, PhD, University of California-Davis

Outcomes & Lessons Learned:

  • Studied a unique concept of controlling prostate cancer cells at the beginning of the checkpoint of multiple signaling pathways that control prostate cancer cell functions, testing several compounds for their ability to block this metabolism and prostate cancer cell growth and spread which may lead to new approaches in developing therapeutic strategies
  • Characterized and confirmed the new function of mEH in hydrolyzing 2-arachidonoylglycerol (2-AG) in various human cells, including human prostate cancer cells, identifying results that supported the hypothesis that mEH has a novel function of hydrolyzing the endocannabinoid, 2-AG
  • Identified that mEH may significantly contribute to the hydrolysis of 2-AG and prostate cancer development and progression
  • Found that hypoxia increased the expression of mEH, implicating that mEH is an important regulator of solid tumors such as prostate cancer
  • Disseminated findings in several publications

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