The effect of Delta(9)-tetrahydrocannabinol (THC), the major psycho-active component of marijuana, in human prostate cancer cells PC-3 was investigated. THC caused apoptosis in a dose-dependent manner, Morphological and biochemical changes induced by THC in prostate PC-3 cells shared the characteristics of an apoptotic phenomenon. First, loss of plasma membrane asymmetry determined by fluorescent anexin V binding. Second, presence of apoptotic bodies and nuclear fragmentation observed by DNA staining with 4',6-diamino-2-phenylindole (DAPI), Third, presence of typical 'ladder-patterned' DNA fragmentation. Central cannabinoid receptor expression vc;as observed in PC-3 cells by immunofluorescence studies, However. several results indicated that the apoptotic effect,vas cannabinoid receptor-independent, such as lack of an effect of the potent cannabinoid agonist WIN 55,212-2, inability of cannabinoid antagonist AM 251 to prevent cellular death caused by THC and absence of an effect of pertussis toxin pre-treatment. (C) 1999 Federation of European Biochemical Societies.