ArticleMolecules (Basel, Switzerland)2008
Effect of dehydroaltenusin-C12 derivative, a selective DNA polymerase alpha inhibitor, on DNA replication in cultured cells.
Article in Molecules (Basel, Switzerland), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 12 citations in OpenAlex.
- Discovery of a novel DNA polymerase inhibitor and characterization of its antiproliferative properties.Cancer biology & therapy · 2019Article
- Oral administration of monogalactosyl diacylglycerol from spinach inhibits colon tumor growth in mice.Experimental and therapeutic medicine · 2013Article
- DNA damage tolerance: a double-edged sword guarding the genome.Translational cancer research · 2013Article
- DNA polymerases and cancer.Nature reviews. Cancer · 2011Review
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dehydroaltenusin is a selective inhibitor of mammalian DNA polymerase alpha (pol alpha) from a fungus (Alternaria tennuis). We have designed, synthesized, and characterized a derivative of dehydroaltenusin conjugated with a C12-alkyl side chain (dehydroaltenusin-C12 [C12]). C12 was the strongest pol alpha inhibitor in vitro. We introduced C12 into NIH3T3 cells with the help of a hypotonic shift, that is, a transient exposure of cultured cells in hypotonic buffer with small molecules which can not penetrate cells. The cells that took in C12 by hypotonic shift showed cell growth inhibition. At a low concentration (5 microM), DNA replication was inhibited and several large replication protein A (RPA) foci, which is different from dUTP foci. Furthermore, when C12 was incubated with aphidicolin, RPA foci were not observed in cells. Finally, these findings suggest that C12 inhibited DNA replication through pol alpha inhibition, and generated single-stranded DNA, resulted in uncoupling of the leading strand and lagging strand synthesis. These findings suggest that C12 could be more interesting as a molecule probe or anticancer agent than aphidicolin. C12 might provide novel markers for the development of antiproliferative drugs.
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Registered trials
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