Oligonucleotides protect cells from the cytotoxicity of several anti-cancer chemotherapeutic drugs.
The possibility of inhibiting gene expression with antisense oligonucleotides (AS ODNs) in combination with more conventional chemotherapy is a very attractive modality in oncology. However, possible interaction between the ODN and drug must be considered. Here we show that ODNs protect cells from the cytostatic/cytotoxic action of actinomycin D (AMD), adriamycin, daunomycin or quinacrine, but not mitomycin, camptothecin, vincristine, cisplatin, etoposide (VP-16) or cycloheximide. The cytoprotective effect depends on ODN length as well as ability to interact directly with the cytotoxic drug and is only slightly sequence selective.
Blagosklonny
M V
MV
Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Neckers
L M
LM
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000633:toxicity*; D001483:Base Sequence; D002470:Cell Survival / Q000187:drug effects; D003609:Dactinomycin / Q000378:metabolism / Q000633:toxicity; D003630:Daunorubicin / Q000378:metabolism / Q000633:toxicity; D004317:Doxorubicin / Q000378:metabolism / Q000633:toxicity; D004347:Drug Interactions; D006801:Humans; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000378:metabolism / Q000627:therapeutic use*; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects
D000970:Antineoplastic Agents; D016376:Oligonucleotides, Antisense; D018124:Receptors, Tumor Necrosis Factor; D003609:Dactinomycin; D004317:Doxorubicin; D003630:Daunorubicin