Antitumor activity of alkaloids derived from Amaryllidaceae species.
The aim of the present study was to investigate the anticancer properties of five alkaloids isolated from Amaryllidaceae, including the inhibitory effect on P-glycoprotein (P-gp) and the apoptosis-inducing capacity. The tested alkaloids were evaluated for their multidrug resistance (MDR)-reversing activity on human MDR1-gene-transfected L5178 mouse lymphoma cells, using the rhodamine-123 (Rh-123) assay. Trisphaeridine and pretazettine increased the intracellular Rh-123 concentration 30- and 50-fold, respectively, as compared to the non-treated cells, and 2-O-acetyllycorine and trisphaeridine were demonstrated by means of the checkerboard method to enhance the antiproliferative activity of doxorubicin on L5178 MDR mouse lymphoma cells. The MTT assay revealed that pretazettine, trisphaeridine and 2-O-acetyllycorine displayed excellent antiproliferative effects on both the human and the mouse cell lines. The apoptosis-inducing activities of selected agents (2-O-acetyllycorine and trisphaeridine) were measured via acridine orange and ethidium bromide dual staining and flow cytometry of the subG1 population.
Department of Pharmacodynamics and Biopharmacy, University of Szeged, H-6720 Szeged, Eötvös u. 6, Hungary. zupko@pharm.u-szeged.hu
István
I
Zupkó
Borbála
B
Réthy
Judit
J
Hohmann
Joseph
J
Molnár
Imre
I
Ocsovszki
George
G
Falkay
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D047151:Amaryllidaceae Alkaloids / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation; D004149:Dioxoles / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004338:Drug Combinations; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D007940:Leukemia L5178 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019668:Liliaceae / Q000737:chemistry*; D051379:Mice; D010617:Phenanthridines / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D020112:Rhodamine 123 / Q000378:metabolism; D014162:Transfection
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D047151:Amaryllidaceae Alkaloids; D000970:Antineoplastic Agents; D004149:Dioxoles; D004338:Drug Combinations; D010617:Phenanthridines; D010936:Plant Extracts; C010766:pretazettine; D020112:Rhodamine 123; C462033:trispheridine; D004317:Doxorubicin