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Updated: Jun 4, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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Cannabidiol Suppresses Metastatic Castration-Resistant Prostate Cancer Progression and Recurrence through Modulating

Ethar A Mudhish1, Hassan Y Ebrahim1, Iman E Helal1,2

  • 1School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, Louisiana 71201, United States.

ACS Pharmacology & Translational Science
|December 19, 2024
PubMed

Insights

(-)-Cannabidiol (CBD) effectively targets the IDO1-Kyn-AhR pathway in metastatic castration-resistant prostate cancer (mCRPC). This nonpsychoactive compound suppressed tumor progression and recurrence in preclinical models.

Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive disease.
  • The indoleamine 2,3-dioxygenase-1 (IDO1)-kynurenine (Kyn)-aryl hydrocarbon receptor (AhR) axis is dysregulated in mCRPC, promoting tumorigenesis.
  • (-)-Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid with demonstrated antitumor effects.

Purpose of the Study:

  • To investigate the potential of CBD as a therapeutic agent for mCRPC.
  • To determine the effect of CBD on the IDO1-Kyn-AhR pathway in prostate cancer.
  • To evaluate the efficacy of CBD in preclinical models of mCRPC.

Main Methods:

  • In vitro studies assessed CBD's effects on prostate cancer cell viability, clonogenicity, and expression of IDO1 and AhR.
  • In vivo studies utilized a xenograft model of mCRPC in nude mice, administering CBD orally.
  • Tumor progression, recurrence after surgical excision, and systemic Kyn levels were monitored.

Main Results:

  • CBD demonstrated potent, dose-dependent inhibition of prostate cancer cell viability and clonogenicity in vitro.
  • CBD treatment reduced IDO1 and AhR expression in prostate cancer cells.
  • Oral CBD administration suppressed mCRPC xenograft progression and recurrence, and significantly reduced systemic Kyn levels in mice.

Conclusions:

  • CBD effectively targets the IDO1-Kyn-AhR axis in prostate cancer.
  • CBD exhibits significant preclinical efficacy in controlling mCRPC progression and recurrence.
  • CBD represents a promising nonpsychoactive phytocannabinoid therapeutic lead for mCRPC by modulating tryptophan catabolism.

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