Modulation of transcription factor--DNA interactions by anticancer drugs.
Anticancer drugs which bind DNA can alter the mechanism of gene transcription regulation. In this paper, we report examples of the ability of DNA-interacting drugs to alter the specific DNA binding and function of well-characterized transcription factors to their consensus DNA sequences. In particular, we have examined the effects of major groove binders such as methylating agents, chloroethylating agents and nitrogen mustards, and also minor groove binders such as distamycin derivatives. The results support the view that alterations of the DNA binding of transcription factors caused by the DNA-interacting agents may play an important role in the antitumor effects of these agents. Work is needed to obtain more highly DNA sequence-specific binders which can act as selective modulators of the transcription of genes involved in the malignant properties of cancer cells.
Broggini
M
M
Laboratory of Cancer Chemotherapy, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
D'Incalci
M
M
D000477:Alkylating Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D002945:Cisplatin / Q000494:pharmacology; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D009150:Mustard Compounds / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D014157:Transcription Factors / Q000187:drug effects* / Q000378:metabolism
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D009150:Mustard Compounds; D014157:Transcription Factors; D004247:DNA; D002945:Cisplatin