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Cannabinoid receptor as a novel target for the treatment of prostate cancer.

Abstract

Cannabinoids, the active components of Cannabis sativa Linnaeus (marijuana) and their derivatives have received renewed interest in recent years due to their diverse pharmacologic activities such as cell growth inhibition, anti-inflammatory effects and tumor regression. Here we show that expression levels of both cannabinoid receptors, CB1 and CB2, are significantly higher in CA-human papillomavirus-10 (virally transformed cells derived from adenocarcinoma of human prostate tissue), and other human prostate cells LNCaP, DUI45, PC3, and CWR22Rnu1 than in human prostate epithelial and PZ-HPV-7 (virally transformed cells derived from normal human prostate tissue) cells. WIN-55,212-2 (mixed CB1/CB2 agonist) treatment with androgen-responsive LNCaP cells resulted in a dose- (1-10 micromol/L) and time-dependent (24-48 hours) inhibition of cell growth, blocking of CB1 and CB2 receptors by their antagonists SR141716 (CB1) and SR144528 (CB2) significantly prevented this effect. Extending this observation, we found that WIN-55,212-2 treatment with LNCaP resulted in a dose- (1-10 micromol/L) and time-dependent (24-72 hours) induction of apoptosis (a), decrease in protein and mRNA expression of androgen receptor (b), decrease in intracellular protein and mRNA expression of prostate-specific antigen (c), decrease in secreted prostate-specific antigen levels (d), and decrease in protein expression of proliferation cell nuclear antigen and vascular endothelial growth factor (e). Our results suggest that WIN-55,212-2 or other non-habit-forming cannabinoid receptor agonists could be developed as novel therapeutic agents for the treatment of prostate cancer.

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    ,

    Department of Dermatology, University of Wisconsin, Madison, Wisconsin 53706, USA.

    , ,

    Source

    Cancer research 65:5 2005 Mar 01 pg 1635-41

    MeSH

    Adenocarcinoma
    Apoptosis
    Benzoxazines
    Calcium Channel Blockers
    Cannabinoids
    Dose-Response Relationship, Drug
    Humans
    Male
    Morpholines
    Naphthalenes
    Neoplasms, Hormone-Dependent
    Piperidines
    Proliferating Cell Nuclear Antigen
    Prostate-Specific Antigen
    Prostatic Neoplasms
    Pyrazoles
    RNA, Messenger
    Receptor, Cannabinoid, CB1
    Receptor, Cannabinoid, CB2
    Receptors, Androgen
    Rimonabant
    Time Factors
    Tumor Cells, Cultured
    Vascular Endothelial Growth Factor A

    Pub Type(s)

    Journal Article
    Research Support, U.S. Gov't, Non-P.H.S.

    Language

    eng

    PubMed ID

    15753356

    Citation

    Sarfaraz, Sami, et al. "Cannabinoid Receptor as a Novel Target for the Treatment of Prostate Cancer." Cancer Research, vol. 65, no. 5, 2005, pp. 1635-41.
    Sarfaraz S, Afaq F, Adhami VM, et al. Cannabinoid receptor as a novel target for the treatment of prostate cancer. Cancer Res. 2005;65(5):1635-41.
    Sarfaraz, S., Afaq, F., Adhami, V. M., & Mukhtar, H. (2005). Cannabinoid receptor as a novel target for the treatment of prostate cancer. Cancer Research, 65(5), pp. 1635-41.
    Sarfaraz S, et al. Cannabinoid Receptor as a Novel Target for the Treatment of Prostate Cancer. Cancer Res. 2005 Mar 1;65(5):1635-41. PubMed PMID: 15753356.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Cannabinoid receptor as a novel target for the treatment of prostate cancer. AU - Sarfaraz,Sami, AU - Afaq,Farrukh, AU - Adhami,Vaqar M, AU - Mukhtar,Hasan, PY - 2005/3/9/pubmed PY - 2005/4/20/medline PY - 2005/3/9/entrez SP - 1635 EP - 41 JF - Cancer research JO - Cancer Res. VL - 65 IS - 5 N2 - Cannabinoids, the active components of Cannabis sativa Linnaeus (marijuana) and their derivatives have received renewed interest in recent years due to their diverse pharmacologic activities such as cell growth inhibition, anti-inflammatory effects and tumor regression. Here we show that expression levels of both cannabinoid receptors, CB1 and CB2, are significantly higher in CA-human papillomavirus-10 (virally transformed cells derived from adenocarcinoma of human prostate tissue), and other human prostate cells LNCaP, DUI45, PC3, and CWR22Rnu1 than in human prostate epithelial and PZ-HPV-7 (virally transformed cells derived from normal human prostate tissue) cells. WIN-55,212-2 (mixed CB1/CB2 agonist) treatment with androgen-responsive LNCaP cells resulted in a dose- (1-10 micromol/L) and time-dependent (24-48 hours) inhibition of cell growth, blocking of CB1 and CB2 receptors by their antagonists SR141716 (CB1) and SR144528 (CB2) significantly prevented this effect. Extending this observation, we found that WIN-55,212-2 treatment with LNCaP resulted in a dose- (1-10 micromol/L) and time-dependent (24-72 hours) induction of apoptosis (a), decrease in protein and mRNA expression of androgen receptor (b), decrease in intracellular protein and mRNA expression of prostate-specific antigen (c), decrease in secreted prostate-specific antigen levels (d), and decrease in protein expression of proliferation cell nuclear antigen and vascular endothelial growth factor (e). Our results suggest that WIN-55,212-2 or other non-habit-forming cannabinoid receptor agonists could be developed as novel therapeutic agents for the treatment of prostate cancer. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/15753356/Cannabinoid_receptor_as_a_novel_target_for_the_treatment_of_prostate_cancer_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15753356 DB - PRIME DP - Unbound Medicine ER -