Increased sensitivity to cytosine arabinoside in human leukemia by c-raf-1 antisense oligonucleotides

Tadao Funato, Kanoko Kozawa, Shinichi Fujimaki, Mitsuo Kaku

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

c-raf-1, a cytoplasmic serine/threonine protein kinase, plays an important role in mitogen- and damage-responsive cellular signal transduction pathways. Expression of c-raf-1 modifies cell growth, proliferation and survival. Although expression of c-raf-1 has been studied in several tumors, the role of c-raf-1 in leukemia is so far unclear. We examined the expression of c-raf-1 in the human leukemia cell lines U937 and K562, and in a cytosine arabinoside (Ara-C)-resistant cell line (K562AC) derived from K562. Expression of c-raf-1 was increased in U937 and in Ara-C-resistant K562AC cells compared with the parental cells. We then investigated whether inhibition of c-raf-1 expression by antisense oligonucleotides increases the sensitivity to Ara-C in U937 and K562AC cells. Antisense oligonucleotides for c-raf-1 inhibited expression of c-raf-1 mRNA, but did not affect cell growth and increased sensitivity to Ara-C but not to other drugs such as adriamycin, VP-16 or vincristine. These results suggest that c-raf-1 is one of the factors involved in Ara-C resistance in leukemia and lend weight to the case for development of anti-cancer therapeutics involving oncogene-targeted antisense oligonucleotides. [

Original languageEnglish
Pages (from-to)325-329
Number of pages5
JournalAnti-cancer drugs
Volume12
Issue number4
DOIs
Publication statusPublished - 2001 May 29

Keywords

  • Antisense oligonucleotides
  • Cytosine arabinside
  • Leukemia
  • c-raf-1

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research

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