Regulation of topoisomerase II expression during the VM-26 induced differentiation of IW32 murine erythroleukemia cells

Sai Koong Tan, Shye Jay Tang, Mei Chih Wang, Jaulang Hwang, Fung Fang Wang

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The effect of VM-26, a topoisomerase II targeting drug, on IW32 murine erythroleukemia cells was investigated. The VM-26 induced IW32 cells to differentiate at a non-toxic but cytostatic concentration (0.01 μg/ml). More than 40% of the cells were induced to synthesize hemoglobin, and cells were arrested in G2/M phase of the cell cycle. Levels of β-globin mRNA also increased significantly. Cells became committed to erythroid maturation after 16 h of continuous drug exposure. Replacement with fresh VM-26 after 48 h of drug treatment further increased the hemoglobin containing cells to greater than 80%. Unlike other drug induced erythroleukemia cell differentiation, c-myc mRNA expression was not affected by VM-26. Inhibition of topoisomerase II activity was observed during the first 12 h of VM-26 treatment; however, elevated enzyme activity was found thereafter. Northern blot analysis showed significant increase in the expression of topoisomerase IIα mRNA at 12 and 24 h after VM-26 addition. These findings indicate that VM-26 inhibited the activity of topoisomerase II and promoted the committed differentiation of IW32 cells along the erythroid pathway. In addition, a parallel increase in mRNA and activity levels of topoisomerase II in differentiated cells suggests that regulation of the enzyme expression occurred in the VM-26 induced erythroid maturation.

Original languageEnglish
Pages (from-to)249-257
Number of pages9
JournalLeukemia Research
Volume20
Issue number3
DOIs
Publication statusPublished - Mar 1996
Externally publishedYes

Keywords

  • Erythroleukemia differentiation
  • Topoisomerase II
  • VM-26

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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