Anguidine potentiates cis-platinum in human brain tumor cells.
Anguidine pretreatment was previously shown to potentiate cis-platinum in Chinese hamster ovary cells by 100-fold, probably by enhancing cellular cis-platinum uptake. Since both cis-platinum and anguidine have been reported to have clinical efficacy in human brain tumors, the present study was initiated to investigate whether anguidine's potentiation of cis-platinum was applicable to human brain tumor cells in culture. Using the colony formation assay, it was found that anguidine enhanced cis-platinum's cytotoxicity by ten-fold, producing a dose modification factor of 1.74. Alkaline elution analysis of cis-platinum-induced DNA cross-links found that anguidine enhanced cross-linking by a factor of 1.55, 1.76, 1.63, and 1.48 at 0, 6, 24, and 48 hr, respectively, after cis-platinum treatment. This enhancement of cross-linking is evidence for anguidine increasing cis-platinum uptake. Thus, anguidine enhances cis-platinum-induced DNA cross-linking and subsequent cytotoxicity in human brain tumor cells, and may be clinically useful in combination with cis-platinum in those tumors.
D001932:Brain Neoplasms / Q000188:drug therapy*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D004247:DNA / Q000378:metabolism; D004357:Drug Synergism; D005910:Glioma / Q000188:drug therapy; D006801:Humans; D066298:In Vitro Techniques; D012717:Sesquiterpenes / Q000627:therapeutic use*; D013997:Time Factors; D014255:Trichothecenes / Q000627:therapeutic use*
D012717:Sesquiterpenes; D014255:Trichothecenes; D004247:DNA; D002945:Cisplatin; C001809:diacetoxyscirpenol