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The endocannabinoid system in prostate cancer

Nature Reviews Urology volume 8, pages 553–561 (2011)Cite this article

Subjects

Abstract

Cannabinoids, their receptors and their metabolizing enzymes are emerging as a new regulatory system, which is involved in multiple physiological functions. Normal prostate tissue expresses several constituents of the endocannabinoid system including the CB1 receptor, receptors belonging to the transient receptor potential family and fatty acid amide hydrolase, a hydrolyzing enzyme, all of which have been localized in the glandular epithelia. Accumulating evidence indicate that the endocannabinoid system is dysregulated in prostate cancer, suggesting that it has a role in prostate homeostasis. Overexpression of several components of the endocannabinoid system correlate with prostate cancer grade and progression, potentially providing a new therapeutic target for prostate cancer. Moreover, several cannabinoids exert antitumoral properties against prostate cancer, reducing xenograft prostate tumor growth, prostate cancer cell proliferation and cell migration. Although the therapeutic potential of cannabinoids against prostate cancer is very promising, future research using animal models is needed to evaluate the influence of systemic networks in their antitumoral action.

Key Points

  • The prostate gland expresses several components of the endocannabinoid system, including the CB1 receptor, TRPV1 receptor and the hydrolyzing enzyme fatty acid amide hydrolase

  • Many of the components of the endocannabinoid system are dysregulated in prostate cancer, and their levels correlate with malignant grade, suggesting that they could be novel prognostic markers

  • Several cannabinoids, including WIN-55,212-2, THC, methanandamide and the CB2 agonist JWH-015, exert antitumoral effects against prostate cancer in vivo and in cultured prostate cancer cell lines

  • Cannabinoids induce cell cycle arrest and apoptosis through ceramide generation and Akt inhibition in cells in vitro

  • Studies have suggested a role for the cannabinoid receptor CB2 in the antiproliferative effect of cannabinoids on prostate cancer cells

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Figure 1: Localization of cannabinoid receptors in healthy prostate tissue.
Figure 2: Signaling mechanisms triggered by cannabinoids in androgen-insensitive prostate cancer cell lines.

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Acknowledgements

This work was supported by Ministerio de Ciencia e Innovación (grant SAF2008-03220), Comunidad de Madrid (grants CCG10-UAH/SAL-5956 and CAM S-SAL-0261-2006), Comunidad Castilla-LaMancha (Grant POII11-0159-0054).

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  1. Department of Biochemistry and Molecular Biology, School of Medicine, University of Alcalá, Alcalá de Henares, Madrid, 28871, Spain

    Inés Díaz-Laviada

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Díaz-Laviada, I. The endocannabinoid system in prostate cancer. Nat Rev Urol 8, 553–561 (2011). https://doi.org/10.1038/nrurol.2011.130

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