Diversity of effects of two antitumor anthracycline analogs on the pathway of activation of PKC in intact human platelets.

Abstract:

:Two antitumor antibiotics doxorubicin and daunorubicin were tested for their ability to influence the activation of protein kinase C in human platelets. Daunorubicin was found to inhibit the phosphorylation of the 40 K PKC substrate induced by thrombin and 12-O-tetradecanoyl-phorbol-13-acetate as well as the phosphorylation of the 20 K protein induced by thrombin. The serotonin release associated to these phosphorylative events was also inhibited by daunorubicin. In contrast the effects of doxorubicin, though inhibitory on the release reaction, were always stimulatory of the phosphorylations. Doxorubicin alone was able to induce the phosphorylation of both 40 K and 20 K phosphoproteins in a concentration-dependent manner. Whereas the stimulation by doxorubicin was not influenced by pretreatment with dibutyryl-cyclic-AMP which inhibits the effects of thrombin, this effect was inhibited by daunorubicin, neomycin and stimulated by the diacylglycerol-kinase inhibitor R 59 022. It is proposed that doxorubicin activates the protein kinase C by causing the breakdown of phosphoinositides.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Lanzi C,Banfi P,Ravagnani F,Gambetta RA

doi

10.1016/0006-2952(88)90702-2

subject

Has Abstract

pub_date

1988-09-15 00:00:00

pages

3497-504

issue

18

eissn

0006-2952

issn

1873-2968

pii

0006-2952(88)90702-2

journal_volume

37

pub_type

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