Abstract
The effects of the antitumor drugs daunorubicin, doxorubicin and their complexes with Fe(III) on phosphoinositide hydrolysis, lipid peroxidation and protein kinase C (PKC) activation were measured in intact human platelets. Doxorubicin and the Fe(III) complexes of both doxorubicin and daunorubicin quickly induced lipid peroxidation [as measured by the thiobarbituric acid (TBA) assay], phosphorylation of the 40 K substance of PKC, and increased levels of phosphatidic acid and inositol phosphates. Fe(III) alone or complexed to acetohydroxamic acid induced high levels of TBA-reactive material but did not affect either PKC activation or phosphoinositide turnover. In contrast, daunorubicin, which was ineffective per se, inhibited all these doxorubicin- and anthracyclines/Fe(III)-induced biochemical events. We suggest that phosphoinositide hydrolysis determined by anthracyclines, and consequently PKC activation, could be due to lipid peroxidation, thus triggering the activity of phospholipase C.
Lingua originale | English |
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pagine (da-a) | 1521-1527 |
Numero di pagine | 7 |
Rivista | Biochemical Pharmacology |
Volume | 43 |
DOI | |
Stato di pubblicazione | Pubblicato - 1992 |
Keywords
- Blood Platelets
- Daunorubicin
- Diglycerides
- Doxorubicin
- Enzyme Activation
- Ferric Compounds
- Humans
- Inositol Phosphates
- Lipid Peroxidation
- Neomycin
- Phosphatidic Acids
- Phosphatidylinositols
- Phosphorylation
- Protein Kinase C