ESPE Abstracts

Androgens play a pivotal role in the pathophysiology of Polycystic Ovary Syndrome (PCOS), a common endocrine disorder affecting adolescent girls. Elevated androgen levels are implicated in the development and progression of PCOS, leading to symptoms such as hirsutism, acne, and irregular menstrual cycles. In patients with PCOS, the inhibition of androgen synthesis presents a therapeutic challenge. Given its crucial role in androgen production, CYP17A1 has become a major target for therapeutic interventions in PCOS. 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. qPCR and western blot results revealed that the drugs had no significant impact on the gene and protein levels of CYP17A1. Additionally, ImageStream analysis with PI staining showed no significant changes in the cell cycle of androgen-sensitive LNCaP cells. 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 managing androgen excess in PCOS. Our study reveals the promise of nanoencapsulated curcumin-piperine as a game-changing method for targeting CYP17A1 to improve therapeutic outcomes in adolescents with PCOS. The synergistic benefits observed in our study open new avenues for addressing the difficulties associated with androgen excess in PCOS. Funding: Cancer Research Switzerland grant number: KFS 5557-02-2022