Inhibitory effect of mitoxantrone on activity of protein kinase C and growth of HL60 cells.

Inhibitory effect of mitoxantrone on activity of protein kinase C and growth of HL60 cells. Research Abstract Details 

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Inhibitory effect of mitoxantrone on activity of protein kinase C and growth of HL60 cells. Abstract Text:

N Takeuchi,T Nakamura,F Takeuchi,E Hashimoto,H Yamamura,

Mitoxantrone, a new anthraquinone, showed inhibitory an effect on protein kinase C (PKC) activity. Its IC50 value was 4.4 micrograms/ml (8.5 microM), which is much lower than those of the well-known anthracyclines daunorubicin and doxorubicin, the IC50 values of which are more than 100 micrograms/ml (> 170 microM). Kinetic studies demonstrated that mitoxantrone inhibited PKC in a competitive manner with respect to histone H1, and its Ki value was 6.3 microM (Ki values of daunorubicin and doxorubicin were 0.89 and 0.15 mM, respectively), and in a non-competitive manner with respect to phosphatidylserine and ATP. Inhibition of phosphorylation by mitoxantrone was observed with various substrates including S6 peptide, myelin basic protein and its peptide substrate derived from the amino-terminal region. Their IC50 values were 0.49 microgram/ml (0.95 microM), 1.8 micrograms/ml (3.5 microM), and 0.82 microgram/ml (1.6 microM), respectively. Mitoxantrone did not markedly inhibit the activity of cyclic AMP-dependent protein kinase, casein kinase I or casein kinase II, at concentrations of less than 10 micrograms/ml. On the other hand, brief exposure (5 min) of HL60 cells to mitoxantrone caused the inhibition of cell growth with an IC50 value of 52 ng/ml (0.1 microM). In HL60 cells, most of the PKC activity (about 90%) was detected in the cytosolic fraction. When HL60 cells exposed to 10 micrograms/ml mitoxantrone for 5 min were observed with fluorescence microscopy, the fluorescence elicited from mitoxantrone was detected in the extranuclear area. These results indicated that mitoxantrone is a potent inhibitor of PKC, and this inhibition may be one of the mechanisms of antitumor activity of mitoxantrone.

Inhibitory effect of mitoxantrone on activity of protein kinase C and growth of HL60 cells. Publishing Authors By Initials

N Takeuchi,T Nakamura,F Takeuchi,E Hashimoto,H Yamamura,

For similar cells: cells, cultured: tumor cells, cultured research abstracts see: cells: cells, cultured: tumor cells, cultured research

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Inhibitory effect of mitoxantrone on activity of protein kinase C and growth of HL60 cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of biochemistry

VOLUME: 112

Page Numbers: 762-7

Journal Abbreviation: J. Biochem.

ISSN: 0021-924X

DAY: 19

MONTH: Dec

YEAR: 1992

Inhibitory effect of mitoxantrone on activity of protein kinase C and growth of HL60 cells. Information

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LANGUAGE: eng

NlmUniqueID: 376600

Inhibitory effect of mitoxantrone on activity of protein kinase C and growth of HL60 cells. Keywords Mesh Terms:

KEYWORDS: Tumor Cells, Cultured

MESH TERMS: isolation & purification

Chemical & Substance for Abstract: Inhibitory effect of mitoxantrone on activity of protein kinase C and growth of HL60 cells. Information

Substance Name: Protein Kinase C

Registry Number: EC 2.7.11.13

Grant and Affiliation Information for Inhibitory effect of mitoxantrone on activity of protein kinase C and growth of HL60 cells.

AFFILIATION: Department of Internal Medicine, Fukui Medical School.

Country: JAPAN

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MEDLINETA: J Biochem

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