Enhancement of androgen receptor expression induced by (R)-methanandamide in prostate LNCaP cells.
It has been recently shown that cannabinoids may regulate the growth of many cell types. In the present work we examined the effect of the anandamide analogue (R)-methanandamide (MET) on androgen-dependent prostate LNCaP cell growth. We found that 0.1 microM MET had a mitogenic effect measured by [(3)H]thymidine incorporation into DNA. The effect exerted by MET was blocked by the cannabinoid receptor antagonists SR141716 (SR1) and SR144528 (SR2) as well as by the phosphoinositide 3-kinase (PI3K) inhibitor LY294002, suggesting an involvement of cannabinoid receptors and the PI3K pathway in the mechanism of MET action. MET treatment of LNCaP cells also induced an up-regulation of androgen receptor expression that was blocked by the two cannabinoid receptor antagonists SR1 and SR2. These results show for the first time that cannabinoids may modify androgen receptor expression in an androgen-dependent cell line and by this mechanism could regulate prostate cell growth.
Sánchez
María G
MG
Department of Biochemistry and Molecular Biology, School of Medicine, Alcalá University, 28871, Madrid, Spain.
Sánchez
Ana M
AM
Ruiz-Llorente
Lidia
L
Díaz-Laviada
Inés
I
D059002:Androgen Receptor Antagonists; D001095:Arachidonic Acids / Q000494:pharmacology*; D002186:Cannabinoids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010880:Piperidines / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011944:Receptors, Androgen / Q000096:biosynthesis* / Q000235:genetics; D000077285:Rimonabant; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D015854:Up-Regulation / Q000187:drug effects
D059002:Androgen Receptor Antagonists; D001095:Arachidonic Acids; D002186:Cannabinoids; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D008934:Mitogens; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010880:Piperidines; D011720:Pyrazoles; D011944:Receptors, Androgen; D014316:Tritium; C088155:methanandamide; D000077285:Rimonabant; D013936:Thymidine