Molecular mechanisms in the antiproliferative action of taxol and tiazofurin

Edith Olah, Bela Csokay, Noemi Prajda, Zsofia Kote-Jarai, Y. Albert Yeh, George Weber

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The molecular antiproliferative effects of taxol and tiazofurin were studied in human K562 leukemia and in MCF-7 breast and OVCAR-5 ovarian carcinoma cell cultures. A single treatment with taxol (2 to 100 nM) or tiazofurin (5 to 20 μM) on K562 leukemia cells resulted in both differentiation program and apoptosis in the same cell culture. Tiazofurin proved to be the most potent inducer of differentiation among the inducers, however, taxol had a major impact on induction of the alterations characteristics of apoptosis. The antiproliferative effect of tiazofurin was mediated by 37 to 85% inhibition of IMP dehydrogenase activity. Both the differentiation and apoptosis induced by tiazofurin were dependent on GTP supply. The induction of differentiation and/or apoptosis was mediated by downregulation of c-myc and Ki-ras oncogenes in all three cell lined treated with tiazofurin (by 2 hr) or taxol (by 24 hr). Combined treatments with tiazofurin and taxol exerted a schedule-dependent, antiproliferative interaction in the cell lines studied. Synergistic inhibition of cell proliferation was observed when cells were pretreated with tiazofurin (10 to 15 μM) for at least 12 hr, then taxol (5 to 15 nM) was added.

Original languageEnglish
Pages (from-to)2469-2477
Number of pages9
JournalAnticancer research
Volume16
Issue number5 A
Publication statusPublished - Sep 1 1996

    Fingerprint

Keywords

  • Apoptosis
  • Differentiation
  • K562
  • MCF-7
  • OVCAR-5
  • Schedule dependency
  • Taxol
  • Tiazofurin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Olah, E., Csokay, B., Prajda, N., Kote-Jarai, Z., Yeh, Y. A., & Weber, G. (1996). Molecular mechanisms in the antiproliferative action of taxol and tiazofurin. Anticancer research, 16(5 A), 2469-2477.