Open AccessIn vitro Enhancement of Antitumor Activity of a Water‐soluble Duocarmycin Derivative, KW‐2189, by Caffeine‐mediated DNA‐repair Inhibition in Human Lung Cancer Cells
Author(s) -
Ogasawara Hayato,
Nishio Kazuto,
Ishida Tomoyuki,
Arioka Hitoshi,
Fukuoka Kazuya,
Saijo Nagahiro
Publication year - 1997
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1997.tb00326.x
Subject(s) - aphidicolin , dna , caffeine , chemistry , cytotoxicity , dna damage , in vitro , biochemistry , microbiology and biotechnology , biophysics , dna synthesis , biology , endocrinology
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 m M ), 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.