The Plant Derived 3-3′-Diindolylmethane (DIM) Behaves as CB2 Receptor Agonist in Prostate Cancer Cellular Models

Paolo Tucci* (Corresponding Author), Iain Brown, Guy S Bewick, Roger G Pertwee, Pietro Marini

*Corresponding author for this work

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3-3′-Diindolylmethane (DIM) is a biologically active dimer derived from the endogenous conversion of indole-3-carbinol (I3C), a naturally occurring glucosinolate found in many cruciferous vegetables (i.e., Brassicaceae). DIM was the first pure androgen receptor antagonist isolated from the Brassicaceae family and has been recently investigated for its potential pharmacological use in prostate cancer prevention and treatment. Interestingly, there is evidence that DIM can also interact with cannabinoid receptors. In this context, by considering the well-known involvement of the endocannabinoid system in prostate cancer, we have pharmacologically characterized the properties of DIM on both CB1 and CB2 cannabinoid receptors in two human prostate cancer cell lines: PC3 (androgen-independent/androgen receptor negative) and LNCaP (androgen-dependent). In the PC3 cell line, DIM was able to activate CB2 receptors and potentially associated apoptotic pathways. On the other hand, although DIM was also able to activate CB2 receptors in the LNCaP cell line, no apoptotic effects were observed. Our evidence confirms that DIM is a CB2 receptor ligand and, moreover, it has a potential anti-proliferative effect on androgen-independent/androgen receptor-negative prostate cancer cells.
Original languageEnglish
Article number3620
Number of pages14
JournalInternational Journal of Molecular Sciences
Issue number4
Publication statusPublished - 11 Feb 2023

Bibliographical note

This research was funded by Friends of Anchor (charity no SC025332, Aberdeen, UK), grant number RGB4100, awarded to Prof R.G. Pertwee (R.P.), Pietro Marini (P.M.) and I. Brown (I.B.).

Data Availability Statement

Data is contained within the article.


  • Male
  • Humans
  • Androgens/metabolism
  • Receptors, Androgen/metabolism
  • Prostatic Neoplasms/metabolism
  • Cell Line
  • Brassicaceae/metabolism
  • prostate cancer
  • CB cannabinoid receptors
  • DIM


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