Share This Article:

Distribution and Possible Function of Cannabinoid Receptor Subtype 1 in the Human Prostate

Abstract Full-Text HTML Download Download as PDF (Size:2238KB) PP. 102-109
DOI: 10.4236/oju.2013.32020    3,760 Downloads   5,691 Views   Citations

ABSTRACT

Background: Cannabinoid receptor subtype 1 (CB1) has a relationship to the proliferation of various cells including malignant tumoral cells. We investigated and compared the expression of CB1 in benign and malignant human prostate tissues and in benign and malignant human prostate cell lines, as well as its function for the proliferation of human prostate cancer cells. Methods: Real-time quantitative PCR was performed to compare its expressions in human prostate tissues (normal, benign hyperplasia, and cancer) and prostate cell lines (3 normal and 3 malignant). For localization of CB1, immunofluorescent staining with rabbit anti-CB1 polyclonal antibodies and tetramethyl isothiocyanate (TRITC)-labeled swine anti-rabbit immunoglobulin (DAKO) were used under fluorescence microscope. To further analyze whether cell death was induced by anandamide (non-selective agonist for CB1/CB2) via a receptor dependent mechanism, the viability of DU145 cells, which is known as androgen-insensitive prostate cancer cell, was measured using MTT assay. Results: CB1mRNA was found to be expressed in the all 3 human prostate tissues, however, CB1 protein was expressed in BPH and low grade malignant PC tissues, but not in high grade malignant PC tissues. CB1 as for cell lines, the expression of CB1 was low in malignant cell lines except for DU145. Anandamide elicited cell death, which was significantly inhibited by AM251 (selective antagonist for CB1), indicating that cell death induced by anandamide in DU145 cells was mediated by CB1. Anandamide time-dependently elicits up-regulation of CB1 in DU145 cells. Conclusions: CB1 may be an inhibitory regulator of androgen-insensitive human prostate cancer epithelial cell growth.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

M. Kamiyama, M. Fukasawa, Y. Takihana, N. Sawada, H. Nakagomi, M. Yoshiyama, I. Araki and M. Takeda, "Distribution and Possible Function of Cannabinoid Receptor Subtype 1 in the Human Prostate," Open Journal of Urology, Vol. 3 No. 2, 2013, pp. 102-109. doi: 10.4236/oju.2013.32020.

References

[1] I. Galve-Roperh, C. Sanchez, M. L. Cortes, T. G. del Pulgar, M. Izquierdo and M. Guzman, “Anti-Tumoral Action of Cannabinoids: Involvement of Sustained Ceramide Accumulation and Extracellular Signal-Regulated Kinase Activation,” Nature Medicine, Vol. 6, No. 3, 2000, pp. 313-319. doi:10.1038/73171
[2] M. Bifulco, C. Laezza, G. Portella, et al., “Control by the Endogenous Cannabinoid System of Ras Oncogene-Dependent Tumor Growth,” Faseb Journal, Vol. 15, No. 14, 2001, pp. 2745-2747.
[3] C. Sanchez, M. L. de Ceballos, T. G. del Pulgar, et al., “Inhibition of Glioma Growth in Vivo by Selective Activation of the CB(2) Cannabinoid Receptor,” Cancer Research, Vol. 61, No. 15, 2001, pp. 5784-5789.
[4] M. L. Casanova, C. Blazquez, J. Martinez-Palacio, et al., “Inhibition of Skin Tumor Growth and Angiogenesis in Vivo by Activation of Cannabinoid Receptors,” Journal of Clinical Investigation, Vol. 111, No. 1, 2003, pp. 43-50.
[5] M. Guzman, “Cannabinoids: Potential Anticancer Agents,” Nature Reviews Cancer, Vol. 3, No. 10, 2003, pp. 745-755. doi:10.1038/nrc1188
[6] T. W. Klein, “Cannabinoid-Based Drugs as Anti-Inflammatory Therapeutics,” Nature Reviews Immunology, Vol. 5, No. 5, 2005, pp. 400-411. doi:10.1038/nri1602
[7] A. C. Howlett, J. M. Qualy and L. L. Khachatrian, “Involvement of Gi in the Inhibition of Adenylate Cyclase by Cannabimimetic Drugs,” Molecular Pharmacology, Vol. 29, No. 3, 1986, pp. 307-313.
[8] W. A. Devane, F. A. Dysarz, 3rd, M. R. Johnson, L. S. Melvin and A. C. Howlett, “Determination and Characterization of a Cannabinoid Receptor in Rat Brain,” Molecular Pharmacology, Vol. 34, No. 5, 1988, pp. 605-613.
[9] L. A. Matsuda, S. J. Lolait, M. J. Brownstein, A. C. Young and T. I. Bonner, “Structure of a Cannabinoid Receptor and Functional Expression of the Cloned cDNA,” Nature, Vol. 346, No. 6284, 1990, pp. 561-564. doi:10.1038/346561a0
[10] C. M. Gerard, C. Mollereau, G. Vassart and M. Parmentier, “Molecular Cloning of a Human Cannabinoid Receptor Which Is Also Expressed in Testis,” Biochemical Journal, Vol. 279, Pt. 1, 1991, pp. 129-134.
[11] S. Galiegue, S. Mary, J. Marchand, et al., “Expression of Central and Peripheral Cannabinoid Receptors in Human Immune Tissues and Leukocyte Subpopulations,” European Journal of Biochemistry, Vol. 232, No. 1, 1995, pp. 54-61. doi:10.1111/j.1432-1033.1995.tb20780.x
[12] A. J. Straiker, G. Maguire, K. Mackie and J. Lindsey, “Localization of Cannabinoid CB1 Receptors in the Human Anterior Eye and Retina,” Investigative Ophthalmology & Visual Science, Vol. 40, No. 10, 1999, pp. 2442-2448.
[13] J. Liu, B. Gao, F. Mirshahi, et al., “Functional CB1 Cannabinoid Receptors in Human Vascular Endothelial Cells,” Biochemical Journal, Vol. 346, Pt. 3, 2000, pp. 835-840. doi:10.1042/0264-6021:3460835
[14] U. Pagotto, G. Marsicano, F. Fezza, et al., “Normal Human Pituitary Gland and Pituitary Adenomas Express Cannabinoid Receptor Type 1 and Synthesize Endogenous Cannabinoids: First Evidence for a Direct Role of Cannabinoids on Hormone Modulation at the Human Pituitary Level,” Journal of Clinical Endocrinology & Metabolism, Vol. 86, No. 6, 2001, pp. 2687-2696. doi:10.1210/jc.86.6.2687
[15] R. G. Pertwee, “Evidence for the Presence of CB1 Cannabinoid Receptors on Peripheral Neurones and for the Existence of Neuronal Non-CB1 Cannabinoid Receptors,” Life Science, Vol. 65, No. 6-7, 1999, pp. 597-605. doi:10.1016/S0024-3205(99)00282-9
[16] S. Munro, K. L. Thomas and M. Abu-Shaar, “Molecular Characterization of a Peripheral Receptor for Cannabinoids,” Nature, Vol. 365, No. 6441, 1993, pp. 61-65. doi:10.1038/365061a0
[17] W. A. Devane, L. Hanus, A. Breuer, et al., “Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor,” Science, Vol. 258, No. 5090, 1992, pp. 1946-1949. doi:10.1126/science.1470919
[18] T. Sugiura, S. Kondo, A. Sukagawa, et al., “2-Arachidonoylglycerol: A Possible Endogenous Cannabinoid Receptor Ligand in Brain,” Biochemical and Biophysical Research Communications, Vol. 215, No. 1, 1995, pp. 89-97. doi:10.1006/bbrc.1995.2437
[19] R. Mechoulam, S. Ben-Shabat, L. Hanus, et al., “Identification of an Endogenous 2-Monoglyceride, Present in Canine Gut, That Binds to Cannabinoid Receptors,” Biochemical Pharmacology, Vol. 50, No. 1, 1995, pp. 83-90. doi:10.1016/0006-2952(95)00109-D
[20] L. Hanus, S. Abu-Lafi, E. Fride, et al., “2-Arachidonyl Glyceryl Ether, an Endogenous Agonist of the Cannabinoid CB1 Receptor,” Proceedings of the National Academy of Sciences, Vol. 98, No. 7, 2001, pp. 3662-3665. doi:10.1073/pnas.061029898
[21] C. C. Felder, A. Nielsen, E. M. Briley, et al., “Isolation and Measurement of the Endogenous Cannabinoid Receptor Agonist, Anandamide, in Brain and Peripheral Tissues of Human and Rat,” FEBS Letters, Vol. 393, No. 2-3, 1996, pp. 231-235. doi:10.1016/0014-5793(96)00891-5
[22] A. Szallasi and V. Di Marzo, “New Perspectives on Enigmatic Vanilloid Receptors,” Trends in Neurosciences, Vol. 23, No. 10, 2000, pp. 491-497. doi:10.1016/S0166-2236(00)01630-1
[23] M. Guzman, C. Sanchez and I. Galve-Roperh, “Control of the Cell Survival/Death Decision by Cannabinoids,” Journal of Molecular Medicine, Vol. 78, No. 11, 2001, pp. 613-625. doi:10.1007/s001090000177
[24] V. Di Marzo, T. Bisogno and L. De Petrocellis, “Anandamide: Some Like It Hot,” Trends in Pharmacological Sciences, Vol. 22, No. 7, 2001, pp. 346-349. doi:10.1016/S0165-6147(00)01712-0
[25] A. Jemal, R. Siegel, E. Ward, et al., “Cancer Statistics, 2006,” CA: A Cancer Journal for Clinicians, Vol. 56, No. 2, 2006, pp. 106-130. doi:10.3322/canjclin.56.2.106
[26] S. R. Denmeade, X. S. Lin and J. T. Isaacs, “Role of Programmed (Apoptotic) Cell Death during the Progression and Therapy for Prostate Cancer,” Prostate, Vol. 28, No. 4, 1996, pp. 251-265. doi:10.1002/(SICI)1097-0045(199604)28:4<251::AID-PROS6>3.0.CO;2-G
[27] D. G. Tang and A. T. Porter, “Target to Apoptosis: A Hopeful Weapon for Prostate Cancer,” Prostate, Vol. 32, No. 4, 1997, pp. 284-293. doi:10.1002/(SICI)1097-0045(19970901)32:4<284::AID-PROS9>3.0.CO;2-J
[28] K. Nithipatikom, M. P. Endsley, M. A. Isbell, et al., “2-Arachidonoylglycerol: A Novel Inhibitor of Androgen-Independent Prostate Cancer Cell Invasion,” Cancer Research, Vol. 64, No. 24, 2004, pp. 8826-8830. doi:10.1158/0008-5472.CAN-04-3136
[29] S. Sarfaraz, F. Afaq, V. M. Adhami and H. Mukhtar, “Cannabinoid Receptor as a Novel Target for the Treatment of Prostate Cancer,” Cancer Research, Vol. 65, No. 5, 2005, pp. 1635-1641. doi:10.1158/0008-5472.CAN-04-3410
[30] S. Sarfaraz, F. Afaq, V. M. Adhami, A. Malik and H. Mukhtar, “Cannabinoid Receptor Agonist-Induced Apoptosis of Human Prostate Cancer Cells LNCaP Proceeds through Sustained Activation of ERK1/2 Leading to G1 Cell Cycle Arrest,” Journal of Biological Chemistry, Vol. 281, No. 51, 2006, pp. 39480-39491. doi:10.1074/jbc.M603495200
[31] L. De Petrocellis, D. Melck, A. Palmisano, et al., “The Endogenous Cannabinoid Anandamide Inhibits Human Breast Cancer Cell Proliferation,” Proceedings of the National Academy of Sciences, Vol. 95, No. 14, 1998, pp. 8375-8380. doi:10.1073/pnas.95.14.8375
[32] D. Melck, D. Rueda, I. Galve-Roperh, L. De Petrocellis, M. Guzman and V. Di Marzo, “Involvement of the cAMP/ Protein Kinase A Pathway and of Mitogen-Activated Protein Kinase in the Anti-Proliferative Effects of Anandamide in Human Breast Cancer Cells,” FEBS Letters, Vol. 463, No. 3, 1999, pp. 235-240. doi:10.1016/S0014-5793(99)01639-7
[33] D. Melck, L. De Petrocellis, P. Orlando, 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, Vol. 141, No. 1, 2000, pp. 118-126. doi:10.1210/en.141.1.118
[34] M. Perez, T. Regan, B. Pflug, J. Lynch and D. Djakiew, “Loss of Low-Affinity Nerve Growth Factor Receptor during Malignant Transformation of the Human Prostate,” Prostate, Vol. 30, No. 4, 1997, pp. 274-279. doi:10.1002/(SICI)1097-0045(19970301)30:4<274::AID-PROS8>3.0.CO;2-L
[35] B. R. Pflug, M. Onoda, J. H. Lynch and D. Djakiew, “Reduced Expression of the Low Affinity Nerve Growth Factor Receptor in Benign and Malignant Human Prostate Tissue and Loss of Expression in Four Human Metastatic Prostate Tumor Cell Lines,” Cancer Research, Vol. 52, No. 19, 1992, pp. 5403-5406.
[36] B. Pflug and D. Djakiew, “Expression of p75NTR in a Human Prostate Epithelial Tumor Cell Line Reduces Nerve Growth Factor-Induced Cell Growth by Activation of Programmed Cell Death,” Molecular Carcinogenesis, Vol. 23, No. 2, 1998, pp. 106-114.
[37] S. Krygier and D. Djakiew, “Neurotrophin Receptor p75(NTR) Suppresses Growth and Nerve Growth FactorMediated Metastasis of Human Prostate Cancer Cells,” International Journal of Cancer, Vol. 98, No. 1, 2002, pp. 1-7.
[38] R. Ramer and B. Hinz, “Inhibition of Cancer Cell Invasion by Cannabinoids via Increased Expression of Tissue Inhibitor of Matrix Metalloproteinases-1,” Journal of the National Cancer Institute, Vol. 100, No. 1, 2008, pp. 59-69.
[39] A. Preet, R. K. Ganju and J. E. Groopman, “Delta9-Tetrahydrocannabinol Inhibits Epithelial Growth Factor-Induced Lung Cancer Cell Migration in Vitro as Well as Its Growth and Metastasis in Vivo,” Oncogene, Vol. 27, No. 3, 2008, pp. 339-346.
[40] G. Czifra, A. Varga, K. Nyeste, et al., “Increased Expressions of Cannabinoid Receptor-1 and Transient Receptor Potential Vanilloid-1 in Human Prostate Carcinoma,” Journal of Cancer Research and Clinical Oncology, Vol. 135, No. 4, 2009, pp. 507-514.

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.