Differential effects of long-chain (sphingoid) bases on the monocytic differentiation of human leukemia (HL-60) cells induced by phorbol ester, 1α,25-dihydroxyvitamin D3, or ganglioside G(M3)

V. L. Stevens, E. F. Winton, E. E. Smith, N. E. Owens, J. M. Kinkade, A. H. Merrill

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32 Scopus citations

Abstract

Conditions were developed to prolong the ability of sphinganine, a potent inhbitor of protein kinase C, to block the phorbol ester-induced adherence of HL-60 cells beyond 24 h. The loss of inhibition after this time seen previously (A.H. Merrill, Jr., A.M. Sereni, V.L. Stevens, Y.A. Hannun, R.M. Bell, and J.M. Kinkade, Jr., J. Biol. Chem., 261:12610-12615, 1986), which appeared to be due to metabolism of this long-chain base, was overcome by supplying sphinganine daily. After 4 days, phorbol myristate acetate-induced adherence was inhibited approximately 50% by sphinganine. Sphinganine significantly decreased the expression of nonspecific esterase induced by phorbol myristate acetate in the nonadherent cells, indicating that other aspects of maturation besides adherence were blocked. The effects of daily sphinganine treatments on the monocytic differentiation induced by 1α,25-dihydroxyvitamin D3 or ganglioside G(M3) were also investigated. The increases in nonspecific esterase expression, nitroblue tetrazolium reduction, and morphological maturation caused by either agent was unaffected by the long-chain base. In addition, the changes in several cell surface antigens caused by 1α,25-dihydroxyvitamin D3 was unaltered by sphinganine. Although phorbol esters, 1α,25-dihydroxyvitamin D3, and ganglioside G(M3) all induce the maturation of HL-60 cells along the monocytic lineage, the finding that sphinganine only affected the differentiation initiated by phorbol esters, in which protein kinase C clearly is a major regulator, suggests that this enzyme does not play a major role in these other pathways of differentiation.

Original languageEnglish
Pages (from-to)3229-3234
Number of pages6
JournalCancer Research
Volume49
Issue number12
StatePublished - Jan 1 1989
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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