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In vitro Enhancement of Antitumor Activity of a Water‐soluble Duocarmycin Derivative, KW‐2189, by Caffeine‐mediated DNA‐repair Inhibition in Human Lung Cancer Cells

Duocarmycins, including KW‐2189, bind in the minor groove of double‐stranded DNA at A‐T‐rich sequences, followed by covalent bonding with N‐3 of adenine in preferred sequences. We examined the effect of DNA‐repair modulators, such as caffeine and aphidicolin, on the cytotoxicity of duocarmycins towa...

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Detalles Bibliográficos
Autores principales: Ogasawara, Hayato, Nishio, Kazuto, Ishida, Tomoyuki, Arioka, Hitoshi, Fukuoka, Kazuya, Saijo, Nagahiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 1997
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921316/
https://www.ncbi.nlm.nih.gov/pubmed/9439677
http://dx.doi.org/10.1111/j.1349-7006.1997.tb00326.x
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author Ogasawara, Hayato
Nishio, Kazuto
Ishida, Tomoyuki
Arioka, Hitoshi
Fukuoka, Kazuya
Saijo, Nagahiro
author_facet Ogasawara, Hayato
Nishio, Kazuto
Ishida, Tomoyuki
Arioka, Hitoshi
Fukuoka, Kazuya
Saijo, Nagahiro
author_sort Ogasawara, Hayato
collection PubMed
description Duocarmycins, including KW‐2189, bind in the minor groove of double‐stranded DNA at A‐T‐rich sequences, followed by covalent bonding with N‐3 of adenine in preferred sequences. We examined the effect of DNA‐repair modulators, such as caffeine and aphidicolin, on the cytotoxicity of duocarmycins towards human lung cancer cells, as determined by dye formation assay. Caffeine (0.5 or 1 mM), but not aphidicolin, enhanced the growth‐inhibitory activity of KW‐2189, DU‐86, and duocarmycin SA. Caffeine inhibited repair of DNA strand breaks induced by KW‐2189, as assayed by the alkaline elution technique. This suggests that duocarmycin‐induced DNA strand breaks, which are potentially lethal to cells, are repaired through a caffeine‐sensitive pathway.
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spelling pubmed-59213162018-05-11 In vitro Enhancement of Antitumor Activity of a Water‐soluble Duocarmycin Derivative, KW‐2189, by Caffeine‐mediated DNA‐repair Inhibition in Human Lung Cancer Cells Ogasawara, Hayato Nishio, Kazuto Ishida, Tomoyuki Arioka, Hitoshi Fukuoka, Kazuya Saijo, Nagahiro Jpn J Cancer Res Rapid Communication Duocarmycins, including KW‐2189, bind in the minor groove of double‐stranded DNA at A‐T‐rich sequences, followed by covalent bonding with N‐3 of adenine in preferred sequences. We examined the effect of DNA‐repair modulators, such as caffeine and aphidicolin, on the cytotoxicity of duocarmycins towards human lung cancer cells, as determined by dye formation assay. Caffeine (0.5 or 1 mM), but not aphidicolin, enhanced the growth‐inhibitory activity of KW‐2189, DU‐86, and duocarmycin SA. Caffeine inhibited repair of DNA strand breaks induced by KW‐2189, as assayed by the alkaline elution technique. This suggests that duocarmycin‐induced DNA strand breaks, which are potentially lethal to cells, are repaired through a caffeine‐sensitive pathway. Blackwell Publishing Ltd 1997-11 /pmc/articles/PMC5921316/ /pubmed/9439677 http://dx.doi.org/10.1111/j.1349-7006.1997.tb00326.x Text en
spellingShingle Rapid Communication
Ogasawara, Hayato
Nishio, Kazuto
Ishida, Tomoyuki
Arioka, Hitoshi
Fukuoka, Kazuya
Saijo, Nagahiro
In vitro Enhancement of Antitumor Activity of a Water‐soluble Duocarmycin Derivative, KW‐2189, by Caffeine‐mediated DNA‐repair Inhibition in Human Lung Cancer Cells
title In vitro Enhancement of Antitumor Activity of a Water‐soluble Duocarmycin Derivative, KW‐2189, by Caffeine‐mediated DNA‐repair Inhibition in Human Lung Cancer Cells
title_full In vitro Enhancement of Antitumor Activity of a Water‐soluble Duocarmycin Derivative, KW‐2189, by Caffeine‐mediated DNA‐repair Inhibition in Human Lung Cancer Cells
title_fullStr In vitro Enhancement of Antitumor Activity of a Water‐soluble Duocarmycin Derivative, KW‐2189, by Caffeine‐mediated DNA‐repair Inhibition in Human Lung Cancer Cells
title_full_unstemmed In vitro Enhancement of Antitumor Activity of a Water‐soluble Duocarmycin Derivative, KW‐2189, by Caffeine‐mediated DNA‐repair Inhibition in Human Lung Cancer Cells
title_short In vitro Enhancement of Antitumor Activity of a Water‐soluble Duocarmycin Derivative, KW‐2189, by Caffeine‐mediated DNA‐repair Inhibition in Human Lung Cancer Cells
title_sort in vitro enhancement of antitumor activity of a water‐soluble duocarmycin derivative, kw‐2189, by caffeine‐mediated dna‐repair inhibition in human lung cancer cells
topic Rapid Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921316/
https://www.ncbi.nlm.nih.gov/pubmed/9439677
http://dx.doi.org/10.1111/j.1349-7006.1997.tb00326.x
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