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The endocannabinoid system in prostate cancer

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

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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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References

  1. Matsuda, L. A., Lolait, S. J., Brownstein, M. J., Young, A. C. & Bonner, T. I. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346, 561–564 (1990).

    Article  CAS  PubMed  Google Scholar 

  2. Kogan, N. M. & Mechoulam, R. Cannabinoids in health and disease. Dialogues Clin. Neurosci. 9, 413–430 (2007).

    PubMed  PubMed Central  Google Scholar 

  3. Pertwee, R. G. et al. International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB and CB. Pharmacol. Rev. 62, 588–631 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Guindon, J. & Hohmann, A. G. The endocannabinoid system and cancer: therapeutic implications. Br. J. Pharmacol. 163, 1447–1463 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Fowler, C. J. et al. Targeting the endocannabinoid system for the treatment of cancer—a practical view. Curr. Top. Med. Chem. 10, 814–827 (2010).

    Article  CAS  PubMed  Google Scholar 

  6. Oesch, S. & Gertsch, J. Cannabinoid receptor ligands as potential anticancer agents—high hopes for new therapies? J. Pharm. Pharmacol. 61, 839–853 (2009).

    CAS  PubMed  Google Scholar 

  7. Alexander, A., Smith, P. F. & Rosengren, R. J. Cannabinoids in the treatment of cancer. Cancer Lett. 285, 6–12 (2009).

    Article  CAS  PubMed  Google Scholar 

  8. Velasco, G. et al. Cannabinoids and gliomas. Mol. Neurobiol. 36, 60–67 (2007).

    Article  CAS  PubMed  Google Scholar 

  9. Vara, D. et al. Anti-tumoral action of cannabinoids on hepatocellular carcinoma: role of AMPK-dependent activation of autophagy. Cell Death Differ. 18, 1099–1111 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Alger, B. E. & Kim, J. Supply and demand for endocannabinoids. Trends Neurosci. 34, 304–315 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hanus, L. et al. 2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor. Proc. Natl Acad. Sci. USA 98, 3662–3665 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Oka, S. et al. Ether-linked analogue of 2-arachidonoylglycerol (noladin ether) was not detected in the brains of various mammalian species. J. Neurochem. 85, 1374–1381 (2003).

    Article  CAS  PubMed  Google Scholar 

  13. Brown, I. et al. Cannabinoid receptor-dependent and -independent anti-proliferative effects of omega-3 ethanolamides in androgen receptor-positive and -negative prostate cancer cell lines. Carcinogenesis 31, 1584–1591 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tan, B. et al. Targeted lipidomics: discovery of new fatty acyl amides. AAPS J. 8, E461–E465 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wang, J. & Ueda, N. Biology of endocannabinoid synthesis system. Prostaglandins Other Lipid Mediat. 89, 112–119 (2009).

    Article  CAS  PubMed  Google Scholar 

  16. Ueda, N., Tsuboi, K., Uyama, T. & Ohnishi, T. Biosynthesis and degradation of the endocannabinoid 2-arachidonoylglycerol. Biofactors 37, 1–7 (2011).

    Article  CAS  PubMed  Google Scholar 

  17. Savinainen, J. R., Saario, S. M. & Laitinen, J. T. The serine hydrolases MAGL, ABHD6 and ABHD12 as guardians of 2-arachidonoylglycerol signalling through cannabinoid receptors. Acta Physiol. (Oxf.) http://dx.doi.org/10.1111/j.1748-17162011.02280.x.

  18. Stark, K., Dostalek, M. & Guengerich, F. P. Expression and purification of orphan cytochrome P450 4X1 and oxidation of anandamide. FEBS J. 275, 3706–3717 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Diaz-Laviada, I. & Ruiz-Llorente, L. Signal transduction activated by cannabinoid receptors. Mini Rev. Med. Chem. 5, 619–630 (2005).

    Article  CAS  PubMed  Google Scholar 

  20. Rozenfeld, R. & Devi, L. A. Regulation of CB1 cannabinoid receptor trafficking by the adaptor protein AP-3. FASEB J. 22, 2311–2322 (2008).

    Article  CAS  PubMed  Google Scholar 

  21. Patel, K. D., Davison, J. S., Pittman, Q. J. & Sharkey, K. A. Cannabinoid CB(2) receptors in health and disease. Curr. Med. Chem. 17, 1393–1410 (2010).

    Article  PubMed  Google Scholar 

  22. Atwood, B. K. & Mackie, K. CB2: a cannabinoid receptor with an identity crisis. Br. J. Pharmacol. 160, 467–479 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Morgan, N. H., Stanford, I. M. & Woodhall, G. L. Functional CB2 type cannabinoid receptors at CNS synapses. Neuropharmacology 57, 356–368 (2009).

    Article  CAS  PubMed  Google Scholar 

  24. Pertwee, R. G. GPR55: a new member of the cannabinoid receptor clan? Br. J. Pharmacol. 152, 984–986 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ross, R. A. The enigmatic pharmacology of GPR55. Trends Pharmacol. Sci. 30, 156–163 (2009).

    Article  CAS  PubMed  Google Scholar 

  26. Okuno, T. & Yokomizo, T. What is the natural ligand of GPR55? J. Biochem. 149, 495–497 (2011).

    Article  CAS  PubMed  Google Scholar 

  27. Schroder, F. H. Prostate cancer around the world. An overview. Urol. Oncol. 28, 663–667 (2010).

    Article  PubMed  Google Scholar 

  28. Quon, H., Loblaw, A. & Nam, R. Dramatic increase in prostate cancer cases by 2021. BJU Int. http://dx.doi.org/10.1111/j.1464-410X.2011.10197.x.

  29. Webber, M. M., Bello, D. & Quader, S. Immortalized and tumorigenic adult human prostatic epithelial cell lines: characteristics and applications Part 2. Tumorigenic cell lines. Prostate 30, 58–64 (1997).

    Article  CAS  PubMed  Google Scholar 

  30. Gratzke, C. et al. Transient receptor potential A1 and cannabinoid receptor activity in human normal and hyperplastic prostate: relation to nerves and interstitial cells. Eur. Urol. 57, 902–910 (2010).

    Article  CAS  PubMed  Google Scholar 

  31. Tokanovic, S., Malone, D. T. & Ventura, S. Stimulation of epithelial CB1 receptors inhibits contractions of the rat prostate gland. Br. J. Pharmacol. 150, 227–234 (2007).

    Article  CAS  PubMed  Google Scholar 

  32. Chung, S. C. et al. A high cannabinoid CB(1) receptor immunoreactivity is associated with disease severity and outcome in prostate cancer. Eur. J. Cancer 45, 174–182 (2009).

    Article  CAS  PubMed  Google Scholar 

  33. Ruiz-Llorente, L. et al. Expression of functionally active cannabinoid receptor CB1 in the human prostate gland. Prostate 54, 95–102 (2003).

    Article  CAS  PubMed  Google Scholar 

  34. Czifra, G. et al. Increased expressions of cannabinoid receptor-1 and transient receptor potential vanilloid-1 in human prostate carcinoma. J. Cancer Res. Clin. Oncol. 135, 507–514 (2009).

    Article  CAS  PubMed  Google Scholar 

  35. Dhanasekaran, S. M. et al. Molecular profiling of human prostate tissues: insights into gene expression patterns of prostate development during puberty. FASEB J. 19, 243–245 (2005).

    Article  CAS  PubMed  Google Scholar 

  36. Wang, J. et al. Expression and secretion of N.-acylethanolamine-hydrolysing acid amidase in human prostate cancer cells. J. Biochem. 144, 685–690 (2008).

    Article  CAS  PubMed  Google Scholar 

  37. Nithipatikom, K. et al. 2-arachidonoylglycerol: a novel inhibitor of androgen-independent prostate cancer cell invasion. Cancer Res. 64, 8826–8830 (2004).

    Article  CAS  PubMed  Google Scholar 

  38. Endsley, M. P. et al. Diverse roles of 2-arachidonoylglycerol in invasion of prostate carcinoma cells: location, hydrolysis and 12-lipoxygenase metabolism. Int. J. Cancer 121, 984–991 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Schuel, H. et al. N-Acylethanolamines in human reproductive fluids. Chem. Phys. Lipids 121, 211–227 (2002).

    Article  CAS  PubMed  Google Scholar 

  40. Sarfaraz, S., Afaq, F., Adhami, V. M. & Mukhtar, H. Cannabinoid receptor as a novel target for the treatment of prostate cancer. Cancer Res. 65, 1635–1641 (2005).

    Article  CAS  PubMed  Google Scholar 

  41. Thors, L. et al. 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 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Fowler, C. J., Hammarsten, P. & Bergh, A. Tumour Cannabinoid CB(1) receptor and phosphorylated epidermal growth factor receptor expression are additive prognostic markers for prostate cancer. PLoS ONE 5, e15205 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  44. Sanchez, M. G., Ruiz-Llorente, L., Sanchez, A. M. & Diaz-Laviada, I. Activation of phosphoinositide 3-kinase/PKB pathway by CB(1) and CB(2) cannabinoid receptors expressed in prostate PC-3 cells. Involvement in Raf-1 stimulation and NGF induction. Cell. Signal. 15, 851–859 (2003).

    Article  CAS  PubMed  Google Scholar 

  45. Olea-Herrero, N., Vara, D., Malagarie-Cazenave, S. & Diaz-Laviada, I. 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 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Pineiro, R., Maffucci, T. & Falasca, M. The putative cannabinoid receptor GPR55 defines a novel autocrine loop in cancer cell proliferation. Oncogene 30, 142–152 (2011).

    Article  CAS  PubMed  Google Scholar 

  47. Andradas, C. et al. The orphan G protein-coupled receptor GPR55 promotes cancer cell proliferation via ERK. Oncogene 30, 245–252 (2011).

    Article  CAS  PubMed  Google Scholar 

  48. Ross, R. A. L-alpha-Lysophosphatidylinositol meets GPR55: a deadly relationship. Trends Pharmacol. Sci. 32, 265–269 (2011).

    Article  CAS  PubMed  Google Scholar 

  49. Balenga, N. A. et al. GPR55 regulates cannabinoid 2 receptor-mediated responses in human neutrophils. Cell Res. http://dx.doi.org/10.1038/cr.2011.60.

  50. Endsley, M. P. et al. Expression and function of fatty acid amide hydrolase in prostate cancer. Int. J. Cancer 123, 1318–1326 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Sarfaraz, S., Afaq, F., Adhami, V. M., Malik, A. & Mukhtar, H. 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 (2006).

    Article  CAS  PubMed  Google Scholar 

  52. Sanchez, M. G., Sanchez, A. M., Ruiz-Llorente, L. & Diaz-Laviada, I. Enhancement of androgen receptor expression induced by (R)-methanandamide in prostate LNCaP cells. FEBS Lett. 555, 561–566 (2003).

    Article  CAS  PubMed  Google Scholar 

  53. Cudaback, E., Marrs, W., Moeller, T. & Stella, N. The expression level of CB1 and CB2 receptors determines their efficacy at inducing apoptosis in astrocytomas. PLoS ONE 5, e8702 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  55. Ligresti, A. et al. Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. J. Pharmacol. Exp. Ther. 318, 1375–1387 (2006).

    Article  CAS  PubMed  Google Scholar 

  56. Ruiz, L., Miguel, A. & Diaz-Laviada, I. Delta9-tetrahydrocannabinol induces apoptosis in human prostate PC-3 cells via a receptor-independent mechanism. FEBS Lett. 458, 400–404 (1999).

    Article  CAS  PubMed  Google Scholar 

  57. Melck, D. et al. Suppression of nerve growth factor Trk receptors and prolactin receptors by endocannabinoids leads to inhibition of human breast and prostate cancer cell proliferation. Endocrinology 141, 118–126 (2000).

    Article  CAS  PubMed  Google Scholar 

  58. Sakaki, K. & Kaufman, R. J. Regulation of ER stress-induced macroautophagy by protein kinase C. Autophagy 4, 841–843 (2008).

    Article  CAS  PubMed  Google Scholar 

  59. Ponnusamy, S. et al. Sphingolipids and cancer: ceramide and sphingosine-1-phosphate in the regulation of cell death and drug resistance. Future Oncol. 6, 1603–1624 (2010).

    Article  CAS  PubMed  Google Scholar 

  60. He, C. & Klionsky, D. J. Regulation mechanisms and signaling pathways of autophagy. Annu. Rev. Genet. 43, 67–93 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Qin, L., Wang, Z., Tao, L. & Wang, Y. ER stress negatively regulates AKT/TSC/mTOR pathway to enhance autophagy. Autophagy 6, 239–247 (2010).

    Article  CAS  PubMed  Google Scholar 

  62. Salazar, M. et al. Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. J. Clin. Invest. 119, 1359–1372 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Diaz-Laviada, I. Effect of capsaicin on prostate cancer cells. Future Oncol. 6, 1545–1550 (2010).

    Article  CAS  PubMed  Google Scholar 

  64. Bradford, P. G. & Awad, A. B. Modulation of signal transduction in cancer cells by phytosterols. Biofactors 36, 241–247 (2010).

    Article  CAS  PubMed  Google Scholar 

  65. Liu, X. et al. Acid ceramidase upregulation in prostate cancer: role in tumor development and implications for therapy. Expert Opin. Ther. Targets 13, 1449–1458 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Turner, L. S. et al. Autophagy is increased in prostate cancer cells overexpressing acid ceramidase and enhances resistance to C6 ceramide. Prostate Cancer Prostatic Dis. 14, 30–37 (2011).

    Article  CAS  PubMed  Google Scholar 

  67. Kuc, C., Jenkins, A. & Van Dross, R. T. Arachidonoyl ethanolamide (AEA)-induced apoptosis is mediated by J-series prostaglandins and is enhanced by fatty acid amide hydrolase (FAAH) blockade. Mol. Carcinog. http://dx.doi.org/10.1002/mc.20770.

  68. Olea-Herrero, N., Vara, D., Malagarie-Cazenave, S. & Diaz-Laviada, I. The cannabinoid R+ methanandamide induces IL-6 secretion by prostate cancer PC3 cells. J. Immunotoxicol. 6, 249–256 (2009).

    Article  CAS  PubMed  Google Scholar 

  69. Xu, M. et al. Regulation of antitumor immune responses by the IL-12 family cytokines, IL-12, IL-23, and IL-27. Clin. Dev. Immunol. http://dx.doi.org/10.1155/2010/832454.

  70. Wilke, C. M. et al. Th17 cells in cancer: help or hindrance? Carcinogenesis 32, 643–649 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Zou, W. & Restifo, N. P. T(H)17 cells in tumour immunity and immunotherapy. Nat. Rev. Immunol. 10, 248–256 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. O'Sullivan, S. E. & Kendall, D. A. Cannabinoid activation of peroxisome proliferator-activated receptors: potential for modulation of inflammatory disease. Immunobiology 215, 611–616 (2010).

    Article  CAS  PubMed  Google Scholar 

  73. Wang, Y. X. PPARs: diverse regulators in energy metabolism and metabolic diseases. Cell Res. 20, 124–137 (2010).

    Article  CAS  PubMed  Google Scholar 

  74. Sun, Y. & Bennett, A. Cannabinoids: a new group of agonists of PPARs. PPAR Res. 2007, 23513 (2007).

  75. Youssef, J. & Badr, M. Peroxisome proliferator-activated receptors and cancer: challenges and opportunities. Br. J. Pharmacol. 164, 68–82 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Nakamura, Y., Suzuki, T., Sugawara, A., Arai, Y. & Sasano, H. Peroxisome proliferator-activated receptor gamma in human prostate carcinoma. Pathol. Int. 59, 288–293 (2009).

    Article  PubMed  Google Scholar 

  77. Hisatake, J. I. et al. Down-regulation of prostate-specific antigen expression by ligands for peroxisome proliferator-activated receptor gamma in human prostate cancer. Cancer Res. 60, 5494–5498 (2000).

    CAS  PubMed  Google Scholar 

  78. Ikezoe, T. et al. Mutational analysis of the peroxisome proliferator-activated receptor gamma gene in human malignancies. Cancer Res. 61, 5307–5310 (2001).

    CAS  PubMed  Google Scholar 

  79. Kubota, T. et al. Ligand for peroxisome proliferator-activated receptor gamma (troglitazone) has potent antitumor effect against human prostate cancer both in vitro and in vivo. Cancer Res. 58, 3344–3352 (1998).

    CAS  PubMed  Google Scholar 

  80. Matsuyama, M. & Yoshimura, R. The target of arachidonic acid pathway is a new anticancer strategy for human prostate cancer. Biologics 2, 725–732 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Nagata, D. et al. Peroxisome proliferator-activated receptor-gamma and growth inhibition by its ligands in prostate cancer. Cancer Detect Prev. 32, 259–266 (2008).

    Article  CAS  PubMed  Google Scholar 

  82. Jiang, M. et al. Disruption of PPARgamma signaling results in mouse prostatic intraepithelial neoplasia involving active autophagy. Cell Death Differ. 17, 469–481 (2010).

    Article  CAS  PubMed  Google Scholar 

  83. Pan, Z., Yang, H. & Reinach, P. S. Transient receptor potential (TRP) gene superfamily encoding cation channels. Hum. Genomics 5, 108–116 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. De Petrocellis, L. et al. Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br. J. Pharmacol. 163, 1479–1494 (2010).

    Article  CAS  Google Scholar 

  85. Akopian, A. N., Ruparel, N. B., Jeske, N. A., Patwardhan, A. & Hargreaves, K. M. Role of ionotropic cannabinoid receptors in peripheral antinociception and antihyperalgesia. Trends Pharmacol. Sci. 30, 79–84 (2009).

    Article  CAS  PubMed  Google Scholar 

  86. Van Haute, C., De Ridder, D. & Nilius, B. TRP channels in human prostate. Scientific World Journal 10, 1597–1611 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Wang, H. P., Pu, X. Y. & Wang, X. H. Distribution profiles of transient receptor potential melastatin-related and vanilloid-related channels in prostatic tissue in rat. Asian J. Androl. 9, 634–640 (2007).

    Article  CAS  PubMed  Google Scholar 

  88. Prevarskaya, N., Skryma, R., Bidaux, G., Flourakis, M. & Shuba, Y. Ion channels in death and differentiation of prostate cancer cells. Cell Death Differ. 14, 1295–1304 (2007).

    Article  CAS  PubMed  Google Scholar 

  89. Du, S. et al. Differential expression profile of cold (TRPA1) and cool (TRPM8) receptors in human urogenital organs. Urology 72, 450–455 (2008).

    Article  PubMed  Google Scholar 

  90. Van der Aa, F., Roskams, T., Blyweert, W. & De Ridder, D. Interstitial cells in the human prostate: a new therapeutic target? Prostate 56, 250–255 (2003).

    Article  PubMed  Google Scholar 

  91. Sanchez, M. G. et al. Expression of the transient receptor potential vanilloid 1 (TRPV1) in LNCaP and PC-3 prostate cancer cells and in human prostate tissue. Eur. J. Pharmacol. 515, 20–27 (2005).

    Article  CAS  PubMed  Google Scholar 

  92. Ziglioli, F. et al. Vanilloid-mediated apoptosis in prostate cancer cells through a TRPV-1 dependent and a TRPV-1-independent mechanism. Acta Biomed. 80, 13–20 (2009).

    CAS  PubMed  Google Scholar 

  93. Maccarrone, M., Lorenzon, T., Bari, M., Melino, G. & Finazzi-Agro, A. Anandamide induces apoptosis in human cells via vanilloid receptors. Evidence for a protective role of cannabinoid receptors. J. Biol. Chem. 275, 31938–31945 (2000).

    Article  CAS  PubMed  Google Scholar 

  94. Guilak, F., Leddy, H. A. & Liedtke, W. Transient receptor potential vanilloid 4: The sixth sense of the musculoskeletal system? Ann. N. Y. Acad. Sci. 1192, 404–409 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Watanabe, H. et al. Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature 424, 434–438 (2003).

    Article  CAS  PubMed  Google Scholar 

  96. Cohen, D. M. TRPV4 and the mammalian kidney. Pflugers Arch. 451, 168–175 (2005).

    Article  CAS  PubMed  Google Scholar 

  97. Tsavaler, L., Shapero, M. H., Morkowski, S. & Laus, R. Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins. Cancer Res. 61, 3760–3769 (2001).

    CAS  PubMed  Google Scholar 

  98. Thebault, S. et al. Novel role of cold/menthol-sensitive transient receptor potential melastatine family member 8 (TRPM8) in the activation of store-operated channels in LNCaP human prostate cancer epithelial cells. J. Biol. Chem. 280, 39423–39435 (2005).

    Article  CAS  PubMed  Google Scholar 

  99. Bai, V. U. et al. Androgen regulated TRPM8 expression: a potential mRNA marker for metastatic prostate cancer detection in body fluids. Int. J. Oncol. 36, 443–450 (2010).

    CAS  PubMed  Google Scholar 

  100. Zhang, L. & Barritt, G. J. Evidence that TRPM8 is an androgen-dependent Ca2+ channel required for the survival of prostate cancer cells. Cancer Res. 64, 8365–8373 (2004).

    Article  CAS  PubMed  Google Scholar 

  101. Romanuik, T. L. et al. LNCaP Atlas: gene expression associated with in vivo progression to castration-recurrent prostate cancer. BMC Med. Genomics 3, 43 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. De Petrocellis, L. et al. Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8. J. Pharmacol. Exp. Ther. 325, 1007–1015 (2008).

    Article  CAS  PubMed  Google Scholar 

  103. Valero, M., Morenilla-Palao, C., Belmonte, C. & Viana, F. Pharmacological and functional properties of TRPM8 channels in prostate tumor cells. Pflugers Arch. 461, 99–114 (2011).

    Article  CAS  PubMed  Google Scholar 

  104. Kulkarni, P. TRPM8 and prostate cancer: to overexpress or repress, that is the question—comment on “Effects of TRPM8 on proliferation and motility of prostate cancer PC-3 cells” by Yang, Z. H. et al. in Asian Journal of Andrology. Asian J. Androl. 11, 150–151 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  105. Yang, Z. H., Wang, X. H., Wang, H. P. & Hu, L. Q. Effects of TRPM8 on the proliferation and motility of prostate cancer PC-3 cells. Asian J. Androl. 11, 157–165 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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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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