TNF increases camptothecin-induced apoptosis by inhibition of NF-κB

P. Valente, D. Arzani, A. Cesario, S. Margaritora, E. Carbone, P. Russo

Research output: Contribution to journalArticle

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Abstract

rHuTNF potentiates CPT-cytotoxicity in human ovarian A2780 cells. In this study, we examined the role of NF-κB in this potentiation. A pulse-labelled DNA study indicated that the combination CPT+TNF had little effect on the rate of DNA elongation at 6 h after drug removal, whereas CPT alone produced a complete inhibition for at least 6 h after drug removal. Flow cytometry analyses showed that CPT+TNF arrested cells in the G 2-M phase, whereas CPT blocked cells in S phase. Looking at the persistence of the NF-κB complexes in cells, it appeared that they were still present at 24 h in TNF-treated cells. In contrast, in CPT-treated cells they persisted for 6 h. In CPT+TNF-treated cells, the NF-κB complexes disappeared quickly and became undetectable at 6 h. The induction of apoptosis was detected only in the CPT+TNF treated cells (using flow cytometry, a filter binding assay and ApopTag staining). These findings show that TNF, in combination with CPT, reduces the time that NF-κB complexes persist in cells likely resulting in the induction of apoptosis.

Original languageEnglish
Pages (from-to)1468-1477
Number of pages10
JournalEuropean Journal of Cancer
Volume39
Issue number10
DOIs
Publication statusPublished - Jul 2003

Fingerprint

Camptothecin
Apoptosis
Flow Cytometry
Gastrin-Secreting Cells
DNA
S Phase
Pharmaceutical Preparations
Cell Division
Staining and Labeling

Keywords

  • Apoptosis
  • Camptothecin
  • Cytotoxicity
  • DNA elongation
  • DNA synthesis cell cycle
  • NF-κB
  • Ovarian cancer cells
  • TNF

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

TNF increases camptothecin-induced apoptosis by inhibition of NF-κB. / Valente, P.; Arzani, D.; Cesario, A.; Margaritora, S.; Carbone, E.; Russo, P.

In: European Journal of Cancer, Vol. 39, No. 10, 07.2003, p. 1468-1477.

Research output: Contribution to journalArticle

Valente, P. ; Arzani, D. ; Cesario, A. ; Margaritora, S. ; Carbone, E. ; Russo, P. / TNF increases camptothecin-induced apoptosis by inhibition of NF-κB. In: European Journal of Cancer. 2003 ; Vol. 39, No. 10. pp. 1468-1477.
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