Inhibition of Chemotactic Peptide–induced PhosphoinositiDe Hydrolysis by Phorbol Esters through the Activation of Protein Kinase C in Differentiated Human Leukemia (HL-60) Cells

Akira Kikuchi, Osamu Kozawa, Yasuo Hamamori, Kozo Kaibuchi, Yoshimi Takai

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Phorbol-12,13-dibutyrate (PDBU), a Tumorpromoting and protein kinase C-activating phorbol ester, inhibited fonnylmethionylleucylphenylalanine–induced generation of inositol mono-, bis-, and tris-phos-phates from the hydrolysis of phosphoinositides in human leukemia (HL-60) cells, which had been differentiated to polymorphonulear leukocyte-like cells by pretreatment with dibutyryl cyclic adenosine 3‘:5’–mono–phosphate. PDBU did not alter the binding of formylmethionylleucylphenylalanine to the cells. Other protein kinase C-activating substances such as 12-O-tetradecanoylphorbol-13-acetate and l-oleoyl-2-acetylglycerol could substitute for PDBU, but 4a-phorbol-12,13-didecanoate, which is inactive for both tumor promotion and protein kinase C activation, was ineffective in this capacity. Prolonged treatment of the cells with PDBU resulted in the down-regulation and decrease of protein kinase C activity to the level of 30-40% of that in the control cells. In the down-regulated cells, formylmethionylleucylphenylalanine still induced generation of the phosphorylated inositols to the same extent as that in the control cells, but the inhibition of this reaction by PDBU was reduced to 30-50% as compared with that in the control cells. These results strongly suggest that Tumorpromoting phorbol esters inhibit the agonist–induced phosphoinosidDe hydrolysis through the activation of protein kinase C in the differentiated HL-60 cells.

Original languageEnglish
Pages (from-to)3401-3406
Number of pages6
JournalCancer Research
Volume46
Issue number7
Publication statusPublished - 01-07-1986
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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