Screening of some saponins and phenolic components of Tribulus terrestris and Smilax excelsa as MDR modulators.
BACKGROUND
Cytotoxic activity of saponins and phenolic compounds have been described in the literature, but no reports were found on their multidrug resistance (MDR)-modulating effects on human mdr1 gene-transfected mouse lymphoma cell line.


METHODS
Methylprototribestin, structurally related compounds and a mixture of 3 acetylated isomers of methylprotodioscin were investigated for antiproliferative effect and modulation of drug accumulation.


RESULTS
The growth inhibitory dose (ID50) of the compounds ranged from 12.64 to 20.62 mug/ml. Methylprototribestin was the most effective resistance modifier. However, methylprotodioscin, pseudoprotodioscin, prosapogenin A of dioscin, tribestin and 5-O-caffeoylshikimic acid showed moderate MDR reversal activity. In a checkerboard method, methyloprototribestin and the mixture of the 3 acetylated isomers enhanced the antiproliferative effects on MDR cells in combination with doxorubicin.


CONCLUSIONS
Based on these results, methylprototribestin and the mixture of the 3 acetylated isomers can be recommended for further in vivo experiments in combination with anthracyclines in human MDR-cancer xenograft transplanted mice.
Ivanova
Antoaneta
A
Institute of Organic Chemistry With Center of Phytochemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Serly
Julianna
J
Dinchev
Dragomir
D
Ocsovszki
Imre
I
Kostova
Ivanka
I
Molnar
Joseph
J
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D016399:Lymphoma, T-Cell; D051379:Mice; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D032281:Smilax / Q000737:chemistry*; D014162:Transfection; D032444:Tribulus / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D010636:Phenols; D010936:Plant Extracts; D012503:Saponins