Natarajan, Ganesan and Malathi, R. and Holler, Eggehard (1999) Increased DNA binding activity of cis-1,1-cyclobutanedicarboxylatodiammineplatinum(II) (Carboplatin) in the presence of nucleophiles and human breast cancer MCF-7 cell cytoplasmic extracts: Activation theory revisited. BIOCHEMICAL PHARMACOLOGY, 58 (10). pp. 1625-1629. ISSN 0006-2952,
Full text not available from this repository. (Request a copy)Abstract
The molecular mechanism of carboplatin [cis-1,1-cyclobutanedicarboxylatodiammineplatinum(II)] activation is still unresolved. We studied the binding of carboplatin to calf thymus DNA in the presence of thiourea, glutathione, and human breast cancer MCF-7 cell cytoplasmic extracts by measurement of DNA-dependent, ethidium bromide fluorescence and atomic absorption spectroscopy. After a 96-hr period of reaction, the decrease in the DNA-dependent fluorescence yield of ethidium bromide due to the formation of platinum (Pt)-DNA adducts increased significantly in the presence of thiourea (6-fold) and glutathione (3- to 4-fold) as compared to the controls in the absence of the nucleophiles. There was also a marked elevation in the levels of platinum incorporated into DNA, measured by atomic absorption spectroscopy (2- to 3-fold and 5- to 7-fold for thiourea and glutathione, respectively). More remarkably, the Pt-DNA adducts formed in the presence of cytoplasmic extracts of MCF-7 human breast cancer cells also showed similar results in a dose-related fashion. Carboplatin, therefore, displayed a characteristic increase in DNA binding/damaging in the presence of the very same S-containing nucleophiles that showed the expected quenching effects in the case of cisplatin [cis-diamminedichloroplatinum (II)]. We propose a nucleophile-facilitated release of the active species of carboplatin prior to binding with DNA. (C) 1999 Elsevier Science Inc.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ANTICANCER-DRUG CARBOPLATIN; CROSS-LINKS; ADDUCT FORMATION; CYTO-TOXICITY; IN-VITRO; PHASE-II; PLATINUM; CISPLATIN; CIS-DIAMMINEDICHLOROPLATINUM(II); PHARMACOKINETICS; carboplatin; drug activation; sulfhydryl groups; MCF-7 extract; platinum-DNA; platinum metabolism |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Alumni or Retired > Prof. Dr. Eggehard Holler |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Dec 2022 06:05 |
| Last Modified: | 13 Dec 2022 06:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48829 |
Actions (login required)
 |
View Item |
