ArticleMolecular cancer therapeutics2009
Induction of glutathione-dependent DNA double-strand breaks by the novel anticancer drug brostallicin.
Article in Molecular cancer therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed, 7 citations in OpenAlex.
- PT-ACRAMTU, a platinum-acridine anticancer agent, lengthens and aggregates, but does not stiffen or soften DNA.Cell biochemistry and biophysics · 2013Article
- Poly(ADP-ribose) polymerase and XPF-ERCC1 participate in distinct pathways for the repair of topoisomerase I-induced DNA damage in mammalian cells.Nucleic acids research · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Brostallicin is a DNA minor groove binder in phase II clinical trials. Here, we show that brostallicin induces gamma-H2AX nuclear foci that colocalize with 53BP1 and are dependent on glutathione, as shown by inhibition of those gamma-H2AX foci by l-buthionine sulfoximine. To differentiate brostallicin from the clinically approved minor groove binder trabectedin (ecteinascidin 743), we tested whether the brostallicin-induced gamma-H2AX and antiproliferative responses were dependent on nucleotide excision repair and found that, unlike trabectedin, they are not. Additionally, brostallicin retained activity in the trabectedin-resistant HCT116-ER5 cell line. Induction of gamma-H2AX foci by brostallicin was partially dependent on the repair nuclease Mre11. Pretreatment with aphidicolin partially reduced brostallicin-induced gamma-H2AX foci, suggesting that brostallicin induces both replication-associated and replication-independent DNA damage. Replication-associated DNA damage was further shown by the colocalization of gamma-H2AX foci with replication foci and by the rapid inhibition of DNA synthesis and accumulation of cells in S phase in response to brostallicin. In addition, brostallicin was able to induce lower intensity gamma-H2AX foci in human circulating lymphocytes. Together, our results indicate that brostallicin induces DNA double-strand breaks and suggest gamma-H2AX as a pharmacodynamic biomarker for brostallicin.
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Registered trials
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