Accession Number : ADA442762


Title :   Cannabinoid Receptors: A Novel Target for Therapy of Prostate Cancer


Descriptive Note : Annual rept. 19 Jan 2004-18 Jan 2005


Corporate Author : WISCONSIN UNIV-MADISON


Personal Author(s) : Mukhtar, Hasan ; Afaq, Farrukh ; Sarfaraz, Sami


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a442762.pdf


Report Date : Feb 2005


Pagination or Media Count : 24


Abstract : Cannabinoids have received renewed interest in recent years due to their diverse pharmacological activities such as cell growth inhibition and tumor regression. Here we show that expression levels of both cannabinoid receptors CB(sub 1) and CB(sub 2) are significantly higher in CA-HPV-10 and other human prostate cells LNCaP, DUI45, PC3, and CWR22RV1 than in human prostate epithelial and PZ-HPV-7 cells. WIN-55,212-2 (mixed CB(sub 1)/CB(SUB 2) agonist) treatment to LNCaP cells resulted in a dose (1-10 muM) and time-dependent (24-48 h) inhibition of cell growth, blocking of CB(sub 1) and CB(SUB 2) receptors by their antagonists SR141716% (CB(sub 1)) and SR144528 (CB(SUB 2)) significantly prevented this effect. Extending this observation we found that WIN-55,212-2 treatment to LNCaP resulted in dose (1-lOmuM) and time-dependent (24-72 h) (i) induction of apoptosis, (ii) decrease in protein and mRNA expression of androgen receptor, (iii) decrease in intracellular protein and mRNA expression of prostate specific antigen (PSA), (iv) decrease in secreted PSA levels, and (v) decrease in protein expression of proliferation cell nuclear antigen and vascular endothelial growth factor. 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.


Descriptors :   *ANTIGENS , *RECEPTOR SITES(PHYSIOLOGY) , *CANNABINOLS , *PROSTATE GLAND , *PROSTATE CANCER , PROTEINS , NEOPLASMS , REGRESSION ANALYSIS , PHARMACOLOGY , ANDROGENS , GROWTH(PHYSIOLOGY) , ENDOTHELIUM , SENSE ORGANS , THERAPY , CELLS(BIOLOGY) , CARDIOVASCULAR SYSTEM


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE