Membrane associated antitumor effects of crocine-, ginsenoside- and cannabinoid derivates.
In the present work a systematic study was initiated with crocine, ginsenoside and cannabinoid derivatives on multidrug resistant mouse lymphoma cells, viral tumor antigen expression and some human leukocyte functions. Among saffron derivatives, crocin and picrocrocin, triglucosyl and diglucosyl crocetin were ineffective on the reversal of multidrug resistance of lymphoma cells. Ginsenoside increased drug accumulation and tumor antigen expression at 2.0-20.0 micrograms/mL. Some cannabinoid derivatives such as cannabinol, cannabispirol and cannabidiol increased drug accumulation, while cannabidiolic acid, delta-9-THC and tetrahydro-cannabidiolic acid reduced drug accumulation of the human mdr1-gene transfected mouse lymphoma cells. The reversal of multidrug resistance is the result of the inhibition of the efflux pump function in the tumor cells. Crocetin esters were less potent than crocin itself in the inhibition of EBV early antigen expression. However crocin and diglucosylcrocetin inhibited early tumor antigen expression of adenovirus infected cells, but triglucosylcrocetin was less effective at 0.01-1.0 microgram/mL. The crocin had no antiviral effect [on HSV-2 infected vero cells] up to 25 micrograms/mL concentration. Ginsenosides had a moderate inhibitory effect except ginsenoside Rb1 (was the less effective) on the drug efflux pump. Among the cannabinoid derivatives the cannabinol and cannabispirol increased drug accumulation, while cannabidiolic acid and delta-8-THC, delta-9-THC and tetrahydro-cannabinol reduced drug accumulation in multidrug resistant mouse lymphoma cells. It is interesting that ginsenosides had a chemical structure-dependent immunomodulating effect by enhancing the activity of NK-cells and ADCC activities.
Molnár
J
J
Institute of Microbiology, Albert Szent-Gyorgyi Medical University, Szeged, Hungary.
Szabó
D
D
Pusztai
R
R
Mucsi
I
I
Berek
L
L
Ocsovszki
I
I
Kawata
E
E
Shoyama
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002186:Cannabinoids / Q000633:toxicity*; D002338:Carotenoids / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects*; D002522:Chlorocebus aethiops; D053138:Cyclohexenes; D013759:Dronabinol / Q000633:toxicity; D018432:Drug Resistance, Multiple; D004354:Drug Screening Assays, Antitumor; D005960:Glucosides / Q000633:toxicity; D006801:Humans; D016399:Lymphoma, T-Cell; D051379:Mice; D005894:Panax / Q000633:toxicity*; D010946:Plants, Medicinal; D012503:Saponins / Q000633:toxicity*; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000633:toxicity; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology; D014709:Vero Cells
D000970:Antineoplastic Agents; D002186:Cannabinoids; D053138:Cyclohexenes; D005960:Glucosides; D012503:Saponins; D013729:Terpenes; D002338:Carotenoids; D013759:Dronabinol; C029036:crocin; D014700:Verapamil; C087962:picrocrocin