Therapeutic Potential of 5α-Reductase Inhibitor 17-oxo-17a-aza-D-homo- 5-androsten-3β-yl phenoxyacetate (17a-aza Steroid) in the Management of Prostate Cancer

Background: The present study highlights the comparative therapeutic efficacy of the newly synthesized drug 17-Oximino-5-androsten-3β-yl 4-aminobenzoate (17a-aza steroid) and finasteride for the treatment of experimentally induced prostate carcinogenesis in rats. Considering the inhibitory activity of the oximes to 5α-reductase and the role of the ester group in augmenting the anti- androgenic property, we decided to synthesize a compound with a lactam moiety in ring D and esters at 3β position of androsterone nucleus as a more potent 5α-reductase inhibitor. Methods: In this study, 30 Sprague Dawley (SD) rats were divided into six groups, viz. Group I as normal controls, Group II was treated with carcinogen N-methyl-N-nitrosourea (MNU) and hormone testosterone propionate (TP) for inducing prostate cancer, Group III rats were treated with finasteride (10 mg/Kg of body weight for 8 weeks through oral gavage), Group IV was treated with 17a-aza steroid (10 mg/Kg of body weight for 8 weeks through oral gavage), whereas, Group V and Group VI were given finasteride and 17a-aza steroid, respectively, with similar doses as in Group III and IV after pretreatment with a carcinogen (MNU) and hormone (TP). Results: The induction of carcinogenesis by treating animals with MNU+TP revealed a significant reduction in weight loss as compared to the normal control group, which, however, increased following 17a-aza steroid treatment. Furthermore, the study witnessed a significant improvement in prostatic biomarker, viz prostatic acid phosphatase (PAcP) in serum following finasteride and 17a-aza steroid treatment to MNU+TP treated rats. Histological investigation of prostate tissue sections of 17a-aza steroid-treated prostate cancer rats showed milder hyperplastic glandular epithelium and exhibited signs of recovery as compared to carcinogen-treated rats. Conclusion: The present findings are preliminary and suggest that the 17a-aza steroid has therapeutic efficacy for the management of experimentally induced prostate cancer, as evidenced by changes in prostate weight, PAcP levels, and histology. In comparison to finasteride, further exploration is needed to assertively conclude its comparative therapeutic efficacy.