Induction of protein-DNA complexes in HeLa S3 cells by KW-2149, a new derivative of mitomycin C.
KW-2149 is a new water-soluble analogue of mitomycin C which shows a broad spectrum antitumor activity in experimental tumor models including mitomycin C-resistant tumors and is less hematotoxic than mitomycin C. We have found that KW-2149 increases protein-DNA complexes in HeLa S3 cells using the potassium/sodium dodecyl sulfate precipitation method which recovers largely DNA bound covalently to protein but does not precipitate DNA bound noncovalently to proteins. In contrast, no increase of the protein-DNA complexes are shown in cells treated with mitomycin C. Thus, KW-2149 binds covalently with both DNA and protein, and this may mediate for KW-2149 the potent and characteristic antitumor activity compared with mitomycin C.
Fujii
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N
Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Japan.
Arai
H
H
Saito
H
H
Kasai
M
M
Nakano
H
H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008623:Mercaptoethanol / Q000494:pharmacology; D016685:Mitomycin / Q000494:pharmacology; D008937:Mitomycins; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000378:metabolism
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D008937:Mitomycins; D009363:Neoplasm Proteins; C057625:KW 2149; D016685:Mitomycin; D008623:Mercaptoethanol; D013936:Thymidine; D002166:Camptothecin