Characterization of Value Nutritions 5-Androstenediol Product and its Proliferative Effects on the LNCaP Cell Line

Grouf, Jaime L

Etd

Characterization of Value Nutritions 5-Androstenediol Product and its Proliferative Effects on the LNCaP Cell Line

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Prostate cancer (Pca) is the number one cancer in U.S. men and a leading cause of cancer-related deaths. The disease is initially dependent upon active male androgens for survival, such as testosterone or dihydrotestosterone. However, relatively inactive androgens like 5-androstenediol (5Adiol) have been considered to play larger roles in disease progression than previously considered. 5Adiol is synthesized in the prostate, is not affected by current anti-androgen therapies, and activates the androgen receptor in human prostate cancer cell lines more effectively than active male androgens. The causal relationship between androgens and prostate cancer progression has significantly risen due to anabolic steroid abuse in competitive sports and recreational athletes. The evidence surrounding an association between androgen abuse and prostate cancer, as well as various other carcinomas, is of great concern within this demographic because of its preventability. Despite their prohibited use, anabolic products continue to be marketed and available for purchase as nutritional supplements. Surveys on current steroid user trends have documented high dosing regimens, extended periods of use, multiple self-diagnosed side effects, and unsafe injection practices. Because few studies have investigated the effects of advertised 5Adiol products on prostate cancer progression, the goal of this study was to investigate whether Value Nutritionâ€™s 5Adiol product possesses comparable mitogenic stimulant activity to testosterone in the androgen-dependent cell line, LNCaP. It should be noted that while this compound is banned by the U.S. Drug Enforcement Administration and is no longer sold through this company, alternative steroids continue to be marketed to consumers. Additional goals included determining whether this product would affect the proliferation of liver cells using the HepG2 cell line, if HepG2 metabolism of the product would play a role in the proliferation of LNCaP cells, and whether the LNCaP cells are capable of converting the 5Adiol product into testosterone. Multiple assays determined that the LNCaP cells were androgen responsive to the 5Adiol product, HepG2 proliferation was stimulated, and HepG2 metabolism of the 5Adiol product increased LNCaP mitogenicity, although significant differences were unattainable primarily due to the LNCaP cells reduced adhesion properties. Because reverse-phase HPLC was unable to detect compounds within 5Adiol even at high concentrations, the mitogenicity observed in both cell lines is unable to be correlated with a particular component in this product. While it is possible that 5Adiol is present at extremely low levels, contamination with other factors, hazardous or not, cannot be ruled out. In conclusion, these results suggest that the use of nutraceuticals have inherent risks for men at risk of developing prostate cancer. The mitogenic effects observed from small levels of unknown compounds in the tested 5Adiol product raise serious questions as to the legitimacy of allowing companies to market and self-regulate their own products.

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