Open AccessPotentiation of Topoisomerase I and II Inhibitors Cell Killing by Tumor Necrosis Factor: Relationship to DNA Strand Breakage Formation
Author(s) -
Orengo Giorgia,
Noviello Elvira,
Cimoli Guido,
Pagnan Gabriella,
Parodi Silvio,
Venturini Marco,
Conte Pier Franco,
Sche Federico,
Conzi Gianfranco,
Russo Patrizia
Publication year - 1992
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.1349-7006.1992.tb02735.x
Subject(s) - topoisomerase , mitoxantrone , etoposide , camptothecin , dna , cytotoxicity , dna damage , amsacrine , biology , microbiology and biotechnology , chemistry , pharmacology , biochemistry , genetics , in vitro , chemotherapy
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.