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

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.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

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

doi

10.1016/s0304-3835(97)00331-5

subject

Has Abstract

pub_date

1997-10-14 00:00:00

pages

201-11

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(97)00331-5

journal_volume

118

pub_type

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