Prostate cancer is the development of cancer in the prostate. Research on the effects of cannabinoids showed an overexpression of cannabinoid receptors on Prostate cancer cells. cannabinoid effects on Prostate cancer cells show a potential therapeutic target to treat this disease.

Literature Discussion: 

Receptors CB1 and CB2 have a high expression in Prostate cancer cells.

This expression increases in the most aggressive cancer cells (Orellana-Serradell et al., 2015; Thors et al., 2010).

Expression of CB1, CB2 and TRPV1 serve as prognostic factor in Prostate cancer cells (Chung et al., 2009; Czifra et al., 2008; Fowler et al., 2010, 2013).

cannabinoids like 2-AG, Anandamide, THC and CBD showed inhibition of Prostate cancer cells through CB1 receptor inducing phosphatase-dependent apoptosis (De Petrocellis et al., 2013; Mimeault et al., 2003; Nithipatikom et al., 2004, 2011; Sreevalsan et al., 2011).

CB1 and CB2 agonists have also anti-proliferative effects in vivo and in vitro models of prostatic cancer cells (De Petrocellis et al., 2013; Mimeault et al., 2003; Nithipatikom et al., 2011; Olea-Herrero et al., 2009a, 2009b).

Novel receptor GPR55 has also been shown to regulate cell proliferation (Piñeiro et al., 2011).

The pathways regulating cannabinoid receptor induced apoptosis and anti-proliferative effects involve Erk and Akt signaling (Cipriano et al., 2013; Orellana-Serradell et al., 2015; Sarfaraz et al., 2006).

Also, synthetic cannabinoids showed apoptosis and anti-proliferation effects through oxidative stress, PPARy and CB1 receptors (Morales et al., 2013; Sarfaraz et al., 2005).

For more information we recommend to read the reviews on the topic from Ramos and Bianco (2012) and Díaz-Laviada (2011).

Literature:

Chung, S.C., Hammarsten, P., Josefsson, A., Stattin, P., Granfors, T., Egevad, L., Mancini, G., Lutz, B., Bergh, A., and Fowler, C.J. (2009). A high cannabinoid CB1 receptor immunoreactivity is associated with disease severity and outcome in Prostate cancer. Eur. J. cancer 45, 174–182.

Cipriano, M., Häggström, J., Hammarsten, P., and Fowler, C.J. (2013). Association between cannabinoid CB1 Receptor Expression and Akt Signalling in Prostate cancer. PLoS ONE 8, e65798.

Czifra, G., Varga, A., Nyeste, K., Marincsák, R., Tóth, B.I., Kovács, I., Kovács, L., and Bíró, T. (2008). Increased expressions of cannabinoid receptor-1 and transient receptor potential vanilloid-1 in human prostate carcinoma. J. cancer Res. Clin. Oncol. 135, 507–514.

De Petrocellis, L., Ligresti, A., Schiano Moriello, A., Iappelli, M., Verde, R., Stott, C.G., Cristino, L., Orlando, P., and Di Marzo, V. (2013). Non-THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms. Br. J. Pharmacol. 168, 79–102.

Díaz-Laviada, I. (2011). The endocannabinoid system in Prostate cancer. Nat. Rev. Urol. 8, 553–561.

Fowler, C.J., Hammarsten, P., and Bergh, A. (2010). Tumour cannabinoid CB1 Receptor and Phosphorylated Epidermal Growth Factor Receptor Expression Are Additive Prognostic Markers for Prostate cancer. PLoS ONE 5, e15205.

Fowler, C.J., Josefsson, A., Thors, L., Chung, S.C., Hammarsten, P., Wikström, P., and Bergh, A. (2013). Tumour epithelial expression levels of endocannabinoid markers modulate the value of endoglin-positive vascular density as a prognostic marker in Prostate cancer. Biochim. Biophys. Acta BBA - Mol. Cell Biol. Lipids 1831, 1579–1587.

Mimeault, M., Pommery, N., Wattez, N., Bailly, C., and Hénichart, J.-P. (2003). Anti-proliferative and apoptotic effects of Anandamide in human prostatic cancer cell lines: Implication of epidermal growth factor receptor down-regulation and ceramide production. The Prostate 56, 1–12.

Morales, P., Vara, D., Goméz-Cañas, M., Zúñiga, M.C., Olea-Azar, C., Goya, P., Fernández-Ruiz, J., Díaz-Laviada, I., and Jagerovic, N. (2013). Synthetic cannabinoid quinones: preparation, in vitro antiproliferative effects and in vivo prostate antitumor activity. Eur. J. Med. Chem. 70, 111–119.

Nithipatikom, K., Endsley, M.P., Isbell, M.A., Falck, J.R., Iwamoto, Y., Hillard, C.J., and Campbell, W.B. (2004). 2-Arachidonoylglycerol A Novel Inhibitor of Androgen-Independent Prostate cancer Cell Invasion. cancer Res. 64, 8826–8830.

Nithipatikom, K., Isbell, M.A., Endsley, M.P., Woodliff, J.E., and Campbell, W.B. (2011). Anti-proliferative effect of a putative endocannabinoid, 2-arachidonylglyceryl ether in prostate carcinoma cells. Prostaglandins Other Lipid Mediat. 94, 34–43.

Olea-Herrero, N., Vara, D., Malagarie-Cazenave, S., and Díaz-Laviada, I. (2009a). The cannabinoid R(+)methAnandamide induces IL-6 secretion by Prostate cancer PC3 cells. J. Immunotoxicol. 6, 249–256.

Olea-Herrero, N., Vara, D., Malagarie-Cazenave, S., and Díaz-Laviada, I. (2009b). Inhibition of human tumour prostate PC-3 cell growth by cannabinoids R(+)-MethAnandamide and JWH-015: Involvement of CB2. Br. J. cancer 101, 940–950.

Orellana-Serradell, O., POBLETE, C.E., SANCHEZ, C., CASTELLÓN, E.A., GALLEGOS, I., HUIDOBRO, C., LLANOS, M.N., and CONTRERAS, H.R. (2015). Proapoptotic effect of endocannabinoids in Prostate cancer cells. Oncol. Rep. 33, 1599–1608.

Piñeiro, R., Maffucci, T., and Falasca, M. (2011). The putative cannabinoid receptor GPR55 defines a novel autocrine loop in cancer cell proliferation. Oncogene 30, 142–152. Ramos, J., and Bianco, F. (2012). The role of cannabinoids in Prostate cancer: Basic science perspective and potential clinical applications. Indian J. Urol. 28, 9.

Sarfaraz, S., Afaq, F., Adhami, V.M., and Mukhtar, H. (2005). cannabinoid Receptor as a Novel Target for the Treatment of Prostate cancer. cancer Res. 65, 1635–1641.

Sarfaraz, S., Afaq, F., Adhami, V.M., Malik, A., and Mukhtar, H. (2006). cannabinoid Receptor Agonist-induced Apoptosis of Human Prostate cancer Cells LNCaP Proceeds through Sustained Activation of ERK1/2 Leading to G1 Cell Cycle Arrest. J. Biol. Chem. 281, 39480–39491.

Sreevalsan, S., Joseph, S., Jutooru, I., Chadalapaka, G., and Safe, S.H. (2011). Induction of Apoptosis by cannabinoids in Prostate and Colon cancer Cells Is Phosphatase Dependent. Anticancer Res. 31, 3799–3807.

Thors, L., Bergh, A., Persson, E., Hammarsten, P., Stattin, P., Egevad, L., Granfors, T., and Fowler, C.J. (2010). Fatty Acid Amide Hydrolase in Prostate cancer: Association with Disease Severity and Outcome, CB1 Receptor Expression and Regulation by IL-4. PLoS ONE 5, e12275.

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