VCOM Louisiana Research Day Program Book 2024

Biomedical Research: Section 2

Ethar A. Mudhish, PharmD; Hassan M. Ebrahim, PhD; Iman E. Hilal, PhD; Abdullah T Alhowiriny, PharmD; Khalid A. El Sayed, PhD Monroe, LA 18 CANNABIDIOL SUPPRESSES PROSTATE CANCER PROGRESSION AND RECURRENCE THROUGH TRYPTOPHAN CATABOLISM

Background: Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive phenotype of prostate cancer (PC). Tryptophan is required for cell growth and biosynthesis of diverse endogenous small peptides and proteins. Tryptophan catabolism produces smaller metabolites play an important role in oncogenesis. Tryptophan oxidative catabolism by indoleamine 2,3-dioxygenase (IDO1) cleaves the indole ring to end up with kynurenine (Kyn). Kyn is an endogenous ligand for aryl hydrocarbon receptors (AhR), and it activates multiple tumorigenesis pathways. IDO1 and AhR occasionally dysregulated in mCRPC PC cell lines. (-)-Cannabidiol (CBD) is a non psychoactive secondary metabolite in Cannabis sativa. Objective: This study explored the CBD PC progression and recurrence suppressive activities. CBD showed potent in vitro dose dependent reduction of the viability and colony formation of PC cells. Methods: Initially, researchers examined the molecular interaction between CBD and IDO1. The effect of CBD was then studied in vitro using a proliferation assay, colony formation assay, migration assay, and western blot. After knocking down the IDO1 gene, the involvement

of IDO1 was examined by testing its effect on colony formation assay. In vivo studies were carried out using two animal models to examine CBD’s effects on progression and recurrence. The KYN plasma level was evaluated from the animal models to validate the molecular target. Results: CBD has been found to reduce the expression of IDO1 and AhR in PC cells. In a study, male athymic nude mice with mCRPC CWR-R1ca-Luc cells xenografted were given a daily 15 mg/kg oral dose of CBD for 30 days, which effectively suppressed the progression of the disease. In another study, mice were given the same CBD oral dose for 45 days after the surgical excision of primary tumors, which suppressed the locoregional and distant recurrences of CWR-R1ca-Luc cells. The serum level of KYN, the IDO1 metabolic product, was significantly reduced in the CBD-treated mice. IDO1 knockdown (KD) in mCRPC CWR-R1ca cells led to the loss of 1/3 of colony formation ability, highlighting the important role of IDO1 in mCRPC motility. Conclusions: The potential of CBD as a lead for controlling mCRPC progression and recurrence cannot be underestimated. By targeting the IDO1/KYN/AhR axis of tryptophan catabolism, CBD has the ability to deliver promising results

in combating this disease. It’s time to explore the benefits of CBD and unlock its full potential in the fight against mCRPC.

31 2024 Via Research Recognition Day