Screening of some saponins and phenolic components of Tribulus terrestris and Smilax excelsa as MDR modulators
Ivanova, A.; Serly, J.; Dinchev, D.; Ocsovszki, I.; Kostova, I.; Molnar, J.
In Vivo 23(4): 545-550
2009
ISSN/ISBN: 0258-851X PMID: 19567388 Document Number: 633543
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. Methylprototribestin, structurally related compounds and a mixture of 3 acetylated isomers of methylprotodioscin were investigated for antiproliferative effect and modulation of drug accumulation. 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. 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.