Type

Journal Article

Authors

R O'Kennedy
D Cooke
P James
D Egan

Subjects

Biochemistry

Topics
animals tumor cells cultured apoptosis dna neoplasm umbelliferones 8 nitro 7 hydroxycoumarin growth inhibitors magnetic resonance spectroscopy cho cells cell survival biosynthesis cell division pharmacology drug effects cricetinae humans cell cycle drug resistance multiple mutagens

Studies on the cytostatic and cytotoxic effects and mode of action of 8-nitro-7-hydroxycoumarin. (1997)

Abstract A derivative of coumarin, 8-nitro-7-hydroxycoumarin (8-NO2-7-OHC), was synthesised, purified and characterised. The cytostatic and cytotoxic nature of this compound was determined using both human and animal cell lines grown in vitro for 96 h in the presence of drug (0-500 microM, equivalent to 0-104 microg/ml). 8-NO2-7-OHC was shown to be cytotoxic to three cell lines, but cytostatic to all cell lines tested. With K562 and HL-60 cells, cell death was found to occur by apoptosis. This cytotoxic effect was found to be irreversible, with cell death continuing to occur following a 96 h recovery period. The cytostatic effects were found to be irreversible in four of the five cell lines tested. 8-NO2-7-OHC demonstrated its cytostatic effects within 24 or 48 h, while its cytotoxic effects appeared more gradually. The IC50 of 8-NO2-7-OHC was 475-880 microM, depending on the cell line tested. It was shown to exert its cytostatic effect through an alteration of cell cycle. It also inhibited DNA synthesis. The toxicity of 8-NO2-7-OHC does not appear to be mediated through the multi-drug resistance (MDR) protein since it caused significant cytostatic and cytotoxic effects to CHrC5 cells, which have an increased expression of this protein. This compound was shown to be non-mutagenic in a standard Ames test, both with or without a mammalian enzyme activation system. The applications and mode of actions of coumarins are discussed.
Collections Ireland -> IT Tallaght -> PubMed

Full list of authors on original publication

R O'Kennedy, D Cooke, P James, D Egan

Experts in our system

1
R O'Kennedy
Dublin City University
Total Publications: 197
 
2
Denise A Egan
IT Tallaght
Total Publications: 44