Membrane associated antitumor effects of crocine-, ginsenoside- and cannabinoid derivates

In the present work a systematic study was initiated with crocine, ginsenos ide and cannabinoid derivatives on multidrug resistant mouse lymphoma cells , vir al tumor antigen expression and some human leukocyte functions. Among saffron derivatives crocin and picrocrocin, triglucosyl and diglucosyl cro cetin were ineffective on the reversal of multidrug resistance of lymphoma cells. Ginsenoside inn-eased drug accumulation and tumor antigen expression at 2.0-20.0 mu g/mL. Some cannabinoid derivatives such as cannabinol, cann abispirol and cannabidiol increased drug accumulation while cannabidiolic a cid, delta-9-THC and tetrahydro-cannabidiolic acid reduced drug accumulatio n of the human mdr1-gene transfected mouse lymphoma cells. The reversal of multidrug resistance is the result of the inhibition of the efflux pump fun ction in the tumor cells. Crocetin eaters were less potent than crocin itse lf in the inhibition of EBV early antigen expression. However crocin and di glucosyl-crocetin inhibited early tumor antigen expression of adenovirus in fected cells, but triglucosylcrocetin was less effective at 0.01-1.0 mu g/m L. The crocin had no antiviral effect [on HSV-2 infected vero cells] rep to 25 mu g/mL concentration. Ginsenosides had a moderate inhibitory effect ex cept ginsenoside Rb1 (was the less effective) on the drug efflux pump. Amon g the cannabinoid derivatives the cannabinol and cannabispirol increased dr ug accumulation, while cannabidiolic acid and delta-9-THC, delta-9-THC and tetrahydro- cannabinol reduced drug accumulation in multidrug resistant mou se lymphoma cells. It is interesting that ginsenosides had a chemical struc ture-dependent immunomodulating effect by enhancing the activity of NK-cell s and ADCC activities.