Inhibition of DNA primase by sphingosine and its analogues parallels with their growth suppression of cultured human leukemic cells

Keiko Tamiya-Koizumi, Takashi Murate, Motoshi Suzuki, Cynthia Marie G. Simbulan, Masako Nakagawa, Masaharu Takemura, Keigo Furuta, Shunji Izuta, Shonen Yoshida

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Sphingosine is a potent inhibitor of a mammalian DNA primase in vitro. Here we measured the inhibition of DNA primase in vitro by 9 sphingosine-analogues with respect to RNA primer synthesis and DNA primase-dependent DNA synthesis, and their potencies of inhibition in vitro were compared with their in vivo effects on human leukemic cells. Sphingosine, phytosphingosine and N, N-dimethylsphingosine strongly inhibited the activity of purified calf thymus DNA primase, and also inhibited the growth of human leukemic cell line HL-60, exerting strong cytotoxicity. Dihydrosphingosine and cis-sphingosine, which showed more subtle inhibition of DNA primase in vitro, moderately inhibited the cell growth in vivo and caused cell death. In contrast, N-acyl-, N-octyl-, and N-acetylsphingosine (ceramides) showing little inhibition of DNA primase suppressed cell growth only slightly. HL 60 cell was arrested at Go/G1 phase by exogenously added sphingosine. From these results, it is suggested that DNA primase is one of targets of sphingosine, an effector molecule in apoptosis.

Original languageEnglish
Pages (from-to)1179-1189
Number of pages11
JournalBiochemistry and Molecular Biology International
Volume41
Issue number6
DOIs
Publication statusPublished - 05-1997

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Genetics

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