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

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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
Publication statusPublished - 01-05-1997
Externally publishedYes

Fingerprint

DNA Primase
Sphingosine
Growth
phytosphingosine
Cell growth
Ceramides
HL-60 Cells
G1 Phase
Cell death
Cytotoxicity
Cell Death
Cells
Apoptosis
Cell Line
Molecules
In Vitro Techniques
DNA

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Tamiya-Koizumi, Keiko ; Murate, Takashi ; Suzuki, Motoshi ; Simbulan, Cynthia Marie G. ; Nakagawa, Masako ; Takemura, Masaharu ; Furuta, Keigo ; Izuta, Shunji ; Yoshida, Shonen. / Inhibition of DNA primase by sphingosine and its analogues parallels with their growth suppression of cultured human leukemic cells. In: Biochemistry and Molecular Biology International. 1997 ; Vol. 41, No. 6. pp. 1179-1189.
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Tamiya-Koizumi, K, Murate, T, Suzuki, M, Simbulan, CMG, Nakagawa, M, Takemura, M, Furuta, K, Izuta, S & Yoshida, S 1997, 'Inhibition of DNA primase by sphingosine and its analogues parallels with their growth suppression of cultured human leukemic cells', Biochemistry and Molecular Biology International, vol. 41, no. 6, pp. 1179-1189.

Inhibition of DNA primase by sphingosine and its analogues parallels with their growth suppression of cultured human leukemic cells. / Tamiya-Koizumi, Keiko; Murate, Takashi; Suzuki, Motoshi; Simbulan, Cynthia Marie G.; Nakagawa, Masako; Takemura, Masaharu; Furuta, Keigo; Izuta, Shunji; Yoshida, Shonen.

In: Biochemistry and Molecular Biology International, Vol. 41, No. 6, 01.05.1997, p. 1179-1189.

Research output: Contribution to journalArticle

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AU - Tamiya-Koizumi, Keiko

AU - Murate, Takashi

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