Affordable Access

Mechanism of cell cycle arrest by sulfoquinovosyl monoacylglycerol with a C18-saturated fatty acid (C18-SQMG).

Authors
  • Murakami, Chikako1
  • Miuzno, Takeshi
  • Hanaoka, Fumio
  • Yoshida, Hiromi
  • Sakaguchi, Kengo
  • Mizushina, Yoshiyuki
  • 1 Laboratory of Food and Nutritional Science, Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, Japan. , (Japan)
Type
Published Article
Journal
Biochemical Pharmacology
Publisher
Elsevier
Publication Date
Apr 01, 2004
Volume
67
Issue
7
Pages
1373–1380
Identifiers
PMID: 15013853
Source
Medline
License
Unknown

Abstract

We have screened the inhibitors of mammalian DNA polymerases from natural products, and in the process found that either sulfoglycolipids or sulfoquinovosyl monoacylglycerol with a C18-saturated fatty acid (C18-SQMG), potently and selectively inhibited the activity of mammalian DNA polymerase (pol) and moderately the pol alpha. C18-SQMG was a cancer cell growth suppressor and a promissive anti-tumor agent. The purpose of this study was to elucidate the cell growth inhibition mechanism of C18-SQMG using HeLa cells. Analyses of the cell cycle and cyclin expression suggested that C18-SQMG arrested the cell cycle at intra-S phase, and the inhibition manner of DNA replication by C18-SQMG was similar to that by hydroxyurea. However, the DNA replication block by C18-SQMG did not induce degradation of Cdc25A protein, which was required for the replication block by hydroxyurea. C18-SQMG somewhat delayed mitosis because it induced phosphorylation of protein kinases, such as checkpoint kinases 1 and 2. These results suggest that C18-SQMG at first blocked DNA replication at the S phase by inhibiting replicative DNA polymerases, such as alpha, and then as the result of the inhibition, the other checkpoint signals associated with the pol might have responded.

Report this publication

Statistics

Seen <100 times