Potentiation of topoisomerase I and II inhibitors cell killing by tumor necrosis factor: relationship to DNA strand breakage formation.
Recombinant human tumor necrosis factor (rHuTNF) synergistically potentiates the cytotoxicity of the topoisomerase I inhibitor camptothecin, and the topoisomerase II inhibitors epidoxorubicin, etoposide, mitoxantrone, ellipticine, actinomycin D and 4'-(9-acridinylamino)methanesulfon-m-anisidide on A2780 human ovarian cancer cell line. Similar synergy was not observed with a combination of rHuTNF and cis-platinum or mitomycin C. When A2780 cells were incubated with rHuTNF simultaneously with camptothecin or mitoxantrone or VP16, increased numbers of DNA single-strand breaks were produced. rHuTNF alone did not induce DNA strand breakage. These data provide evidence that the enhancing effect of rHuTNF is closely related to the DNA damage mediated by topoisomerase-targeted drugs. These observations may have relevance for ovarian cancer treatment.
Orengo
G
G
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Noviello
E
E
Cimoli
G
G
Pagnan
G
G
Parodi
S
S
Venturini
M
M
Conte
P
P
Schenone
F
F
Conzi
G
G
Russo
P
P
D002166:Camptothecin / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage / Q000502:physiology*; D004273:DNA, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D015251:Epirubicin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology; D011994:Recombinant Proteins / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004273:DNA, Neoplasm; D011994:Recombinant Proteins; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014409:Tumor Necrosis Factor-alpha; D015251:Epirubicin; D016685:Mitomycin; D005047:Etoposide; D002945:Cisplatin; D002166:Camptothecin