7906 Nanoencapsulated Curcumin-Piperine Complex: A Breakthrough in Targeting CYP17A1 for Castration Resistant Prostate Cancer Therapy

Abstract Disclosure: J. Yakubu: None. Nanoencapsulated Curcumin-Piperine Complex: A Breakthrough in Targeting CYP17A1 for Castration Resistant Prostate Cancer Therapy. Jibira Yakubu a,b,c, Oya Taritd, Evangelos Natsaridisd, Amit V. Pandey a,ba Translational Hormone Research Program, Department of Biomedical Research, Faculty of Medicine, b Paediatric Endocrinology, Diabetology and Metabolism, University Children’s Hospital, Inselspital, Bern, c Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland. d Biointerfaces, Institute of Chemistry and Bioanalytics, University of Life Sciences FHNW, Muttenz, Switzerland. Abstract: Androgens play a pivotal role in prostate cell survival and are implicated in both early-stage and advanced, castration-resistant prostate cancer (CRPC). In CRPC patients on CYP17A1 inhibitors, the development of drug resistance and hypertensive crisis through the inhibition of CYP21A2 and or its substrate are a recognized challenge. Given its crucial role in androgen production, CYP17A1 has become a major target for cancer therapies. In this study, we employed a mini-evaporation technique to nanoencapsulate curcumin, exploring its impact on CYP17A1 activity in human adrenal NCI-H295R cells. We performed steroid profiling with LC-MS, as well as gene and protein expression studies. Initial results demonstrated that curcumin nanoparticles exhibited superior efficacy in reducing CYP17A1 activity compared to known drug Abiraterone acetate. Curcumin and piperine combined in nano-capsules greatly increased the inhibitory effects on CYP17A1 activity. Furthermore, ongoing studies include western blot investigation of the drug's interaction with the CYP17A1 protein and cell cycle effects. We confirmed the efficacy of our nano formulation by testing its impact on the growth of androgen-sensitive prostate cancer cell lines. Notably, nanoencapsulation improved curcumin's inhibitory effects on DHEA production via CYP17A1. Surprisingly, the curcumin-piperine nano-capsules enhanced these effects while having no effect on CYP21A2, offering a promising option for prostate cancer treatment. Our study reveals the promise of nanoencapsulated curcumin-piperine as a game-changing method for targeting CYP17A1 for improved prostate cancer therapy. The synergistic benefits observed in our study open new avenues for addressing the difficulties associated with androgen deprivation therapy. Funding: Cancer Research Switzerland grant number: KFS 5557-02-2022 Presentation: 6/3/2024