Synergistic Enhancement by Tumor Necrosis Factor of in Vitro Cytotoxicity-group from Chemotherapeutic Drugs Targeted at DNA Topoisomerase II

Richard B. Alexander, William G. Nelson, Donald S. Coffey

Research output: Contribution to journalArticle

Abstract

Recombinant human tumor necrosis factor (rHTNF) alone had no effect on L929 tumor cells at 100 units/ml for 20 h of continuous exposure. However, under the same conditions, rHTNF markedly enhanced the cytotoxicity of Adriamycin, actinomycin D, 4' -(9-acridinylamino)-methanesulfon-m-anisidide, teniposide (VM 26), and etoposide (VP 16), all targeted at DNA topoisomerase II. The rHTNF had a minimally enhancing effect on the cytotoxicity-group of bleomycin, hydroxyurea, and 1-β-D-arabinofuranosylcytosine and no effect on the cytotoxicity-group of cis-platinum, mitomycin C, vincristine, and vinblastine, all chemotherapeutic drugs with dose-related cytotoxic effects on L929 cells but mechanisms of action which do not appear to involve topoisomerase II. Treatment with rHTNF first and then topoisomerase-targeted drugs yielded no enhanced cytotoxicity-group, whereas pretreatment with drug followed by rHTNF yielded marked enhancement of cytotoxicity-group. Topoisomerases have previously been implicated in cell kill phenomena following treatment with certain chemotherapeutic agents [K. M. Tewey, et al. Science (Wash. DC), 226:466-468,1984). The data suggest that the lethality to the cell from topoisomerase-targeted drug treatment is increased by rHTNF in vitro. We suggest that rHTNF may be a useful adjuvant to this class of drugs which has well-known antitumor activity.

Original languageEnglish (US)
Pages (from-to)2403-2406
Number of pages4
JournalCancer Research
Volume47
Issue number9
StatePublished - May 1 1987

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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