Sebastian Powell

Prostate Cancer can take multiple forms, including Benign Prostatic Hyperplasia, or a malignant androgen independent adenocarcinoma. It has become the 2^nd leading cause of cancer-related deaths in men in the United States and is the most common cancer in men above 50 years old. ^1,2  Standard therapy for treatment of Prostate cancer has been with Androgen Deprivation Therapy.³ Yet, once the cancer becomes androgen independent, this therapy no longer has any effect and surgical interventions are not always possible.⁴ With such a high incidence in the US population, there have been continued attempts to discover more efficacious methods in prevention and treatment of the different types of Prostate Cancer. An area that has shown promise, includes the use of Ellagitannin metabolites. Ellagitannins are polyphenol compounds found in many different fruits, nuts, and vegetables including pomegranate juice and walnuts making them readily available through a person’s diet.^5,6 The ellagitannin is hydrolyzed within the gastrointestinal tract to become Ellagic Acid, which is then further metabolized by an individual’s gut flora into different metabotypes of Urolithin (Urolithin A, B, C, and D). It is also important to note that an individual’s microbiota determines the concentrations of each metabotype produced because each has different therapeutic effects. For example, Urolithin A and B have a tendency to accumulate in the prostate.⁷ Previous evidence has shown how these ellagitannin metabolites disrupt the regulatory mechanisms in G1 of the cell cycle upregulating apoptotic effects.⁴ This has led to further study and experiments that have shown how Urolithins promote the CDKN1A gene that produces the regulatory protein p21, activate the Caspase apoptic pathway, and certain metabotypes can Eph-Ephrin system to control the proliferation of epithelial cells.^7,8,9 Urolithins can also decrease the serum concentration of Prostate Specific Antigen as well as Androgen Receptor levels.⁵ These cumulative effects, if harnessed, show a great potential for alternative/adjunct treatments of prostate cancer.

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2. Vanella L, Giacomo D, Claudia, et al. Apoptotic markers in a prostate cancer cell line: Effect of ellagic acid. Oncology Reports. 2013;30(6):2804-2810.
3. Molecular Model for Neuroendocrine Prostate Cancer Progression – Chen – – BJU International – Wiley Online Library. https://onlinelibrary.wiley.com.ezproxy.library.tamu.edu/doi/abs/10.1111/bju.14207. Accessed March 26, 2018.
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7. Giorgio C, Mena P, Rio DD, et al. The ellagitannin colonic metabolite urolithin D selectively inhibits EphA2 phosphorylation in prostate cancer cells. Molecular Nutrition & Food Research. 2015;59(11):2155-2167. doi:10.1002/mnfr.201500470
8. Naiki-Ito A, Chewonarin T, Tang M, et al. Ellagic acid, a component of pomegranate fruit juice, suppresses androgen-dependent prostate carcinogenesis via induction of apoptosis. Prostate. 2015;75(2):151-160. doi:10.1002/pros.22900
9. González-Sarrías A, Núñez-Sánchez MÁ, Tomé-Carneiro J, Tomás-Barberán FA, García-Conesa MT, Espín JC. Comprehensive characterization of the effects of ellagic acid and urolithins on colorectal cancer and key-associated molecular hallmarks: MicroRNA cell specific induction of CDKN1A (p21) as a common mechanism involved. Molecular Nutrition & Food Research. 2016;60(4):701-716. doi:10.1002/mnfr.201500780