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

Fingerprint

Teniposide
Type II DNA Topoisomerase
Leukemia, Erythroblastic, Acute
Messenger RNA
Cell Differentiation
Hemoglobins
Pharmaceutical Preparations
Erythroid Cells
Globins
G2 Phase
Cytostatic Agents
Enzymes
Drug Delivery Systems
Northern Blotting
Cell Division
Cell Cycle

Keywords

  • Erythroleukemia differentiation
  • Topoisomerase II
  • VM-26

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Regulation of topoisomerase II expression during the VM-26 induced differentiation of IW32 murine erythroleukemia cells. / Tan, Sai Koong; Tang, Shye Jay; Wang, Mei Chih; Hwang, Jaulang; Wang, Fung Fang.

In: Leukemia Research, Vol. 20, No. 3, 03.1996, p. 249-257.

Research output: Contribution to journalArticle

Tan, Sai Koong ; Tang, Shye Jay ; Wang, Mei Chih ; Hwang, Jaulang ; Wang, Fung Fang. / Regulation of topoisomerase II expression during the VM-26 induced differentiation of IW32 murine erythroleukemia cells. In: Leukemia Research. 1996 ; Vol. 20, No. 3. pp. 249-257.
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