Abstract
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 crosslinks 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.
Original language | English (US) |
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Pages (from-to) | 343-348 |
Number of pages | 6 |
Journal | Journal of Neuro-Oncology |
Volume | 3 |
Issue number | 4 |
DOIs | |
State | Published - Dec 1986 |
Externally published | Yes |
Keywords
- DNA cross-linking
- anguidine
- brain tumors
- cis-platinum
ASJC Scopus subject areas
- Clinical Neurology
- Neurology
- Oncology
- Cancer Research