VCOM Louisiana Research Day Program Book 2024

Biomedical Research: Section 2

Tanya Kumar, OMS-III; Dalal Dawud, BPharm; Zakaria Y. Abd Elmageed, PhD Monroe, LA 15 TREATMENT OF ESCALATING CONCENTRATIONS OF CHLORPROMAZINE-SENSITIZED CASTRATION-RESISTANT PROSTATE CANCER CELLS TO ENZALUTAMIDE

Background: Prostate cancer (PCa) is the second leading cause of male-related cancer mortality in the United States. Androgens serve as the primary driving force for PCa progression and metastasis. As a result, androgen ablation therapy stands as the conventional treatment method for individuals diagnosed with primary PCa. However, a substantial number of patients develop more aggressive castration-resistant PCa (CRPC). To address CRPC, antiandrogens such as enzalutamide (Xtandi©) are considered first-line treatment. However, most patients develop resistance to enzalutamide requiring them to discontinue the medication. Chlorpromazine (CPZ), an antipsychotic agent known to inhibit clathrin-mediated endocytosis has been associated with a reduced risk of PCa. Objective: The main objective of this study was to evaluate the effect of combining CPZ with enzalutamide in CRPC cells to reduce the development of enzalutamide resistance and improve clinical outcomes. Methods: Cell viability, colony formation, and scratch assays were used to determine cell proliferation and migration of enzalutamide resistant and parental LAPC4 cells. Immunoblotting was performed on individual

and combined treatments over the course of 48 hour time points. Results: Individual treatments of CPZ and enzalutamide exerted anti-proliferative and anti-migratory effects. When combined, CPZ and enzalutamide displayed a synergistic effect in mitigating resistant LAPC4 as compared to sensitive cells. Conclusions: By targeting androgen receptors and clathrin-mediated endocytosis pathways, combined therapy of enzalutamide and CPZ may circumvent resistance that compromises the efficacy of enzalutamide therapy when used as monotherapy.

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