9‐nitro‐camptothecin delays growth of U‐937 leukemia tumors in nude mice and is cytotoxic or cytostatic for human myelomonocytic leukemia lines in vitro

P. Pantazis, J. T. Mendoza, J. A. Early, A. J. Kozielski, Ethan Natelson, B. C. Giovanella

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

The camptothecin derivatives 9-nitro-camptothecin (9NC) and 9-amino-camptothecin (9AC) inhibit similarly growth of HL-60, KG-1, and U-937 cells in vitro, whereas growth of THP-1 cells is inhibited by 9AC, but not by 9NC. Growth inhibition is accompanied by enlargement of cells which contain one (HL-60, THP-1) or more (KG-1, U-937) nuclei. Flow cytometry studies showed that 9NC-treated HL-60 and U-937 cells accumulate in the S and G2 phases of the cell cycle; then they die by apoptosis, with the HL-60 cells being more sensitive than U-937 cells to 9NC. In contrast, 9NC-treated KG-1 and THP-1 cells accumulate in S and G2 phases, but resist death by apoptosis. Of the cell lines tested, only U-937 cells xenografted in nude mice generated subcutaneous myeloid tumors, which exhibited a delayed growth in the presence of 9NC. Further, 9NC-treated advanced U-937 tumors regressed temporarily, indicating that U-937 cells consist of 9NC-sensitive and 9NC-resistant populations.

Original languageEnglish (US)
Pages (from-to)81-89
Number of pages9
JournalEuropean Journal of Haematology
Volume50
Issue number2
DOIs
StatePublished - Jan 1 1993

Keywords

  • cell cycle
  • leukemia tumors
  • myeloid cells
  • nude mouse

ASJC Scopus subject areas

  • Hematology

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