Effects of genistein on growth and differentiation of NB4 human acute promyelocytic leukemia cells

Chunhong Yan, Chen Xiaoguang, Yuan Shoujun, Li Yan, Han Rui

Research output: Contribution to journalArticle

Abstract

AIM: To investigate the possible actions of isoflavone genistein in inducing apoptosis and differentiation of NB4 leukemia cells. METHODS: NBT dye reduction ability was used as the biomarker of differentiation of NB4 cells. Apoptosis was assayed through genomic DNA gel electrophoresis. Expression of bcl-2 gene and DNA topoisomerase II activity were examined with Northern blot analysis and plasmid DNA breakage analysis, respectively. RESULTS: Genistein (40 μmol·L-1) significantly suppressed the growth of NB4 cells, while a large amount of cells died with the prolongation of the drug exposure time. At concentration larger than 40 μmol·L-1, genistein induced condensation of chromatin, breakage of nucleus, and appearance of DNA ladder after agarose electrophoresis in NB4 cells. In consistent with the induction of apoptosis, genistein inhibited expression of bcl-2 gene. At 10 ∼ 200 μmol·L-1, genistein stimulated the topoisomerase II-mediated DNA breakage. On the other hand, genistein induced increase of NBT positive cell number, but the positive rates were lower than 50%. CONCLUSION: Genistein inhibited the growth of NB4 cells through induction of apoptosis and cell death. The mechanism of action might be associated with suppression of DNA topoisomerase II activity. Induction of differentiation may contribute little to the therapeutic activities of genistein in leukemia cells.

Original languageEnglish (US)
Number of pages1
JournalYaoxue Xuebao
Volume35
Issue number4
StatePublished - Apr 1 2000
Externally publishedYes

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Acute Promyelocytic Leukemia
Genistein
Growth
Type II DNA Topoisomerase
Apoptosis
bcl-2 Genes
Electrophoresis
DNA
Leukemia
Isoflavones
Northern Blotting
Sepharose
Chromatin
Cell Differentiation
Plasmids
Cell Death
Coloring Agents
Cell Count
Biomarkers
Gels

Keywords

  • Apoptosis
  • Differentiation
  • Genistein
  • Leukemia cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Effects of genistein on growth and differentiation of NB4 human acute promyelocytic leukemia cells. / Yan, Chunhong; Xiaoguang, Chen; Shoujun, Yuan; Yan, Li; Rui, Han.

In: Yaoxue Xuebao, Vol. 35, No. 4, 01.04.2000.

Research output: Contribution to journalArticle

Yan, Chunhong ; Xiaoguang, Chen ; Shoujun, Yuan ; Yan, Li ; Rui, Han. / Effects of genistein on growth and differentiation of NB4 human acute promyelocytic leukemia cells. In: Yaoxue Xuebao. 2000 ; Vol. 35, No. 4.
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AU - Rui, Han

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N2 - AIM: To investigate the possible actions of isoflavone genistein in inducing apoptosis and differentiation of NB4 leukemia cells. METHODS: NBT dye reduction ability was used as the biomarker of differentiation of NB4 cells. Apoptosis was assayed through genomic DNA gel electrophoresis. Expression of bcl-2 gene and DNA topoisomerase II activity were examined with Northern blot analysis and plasmid DNA breakage analysis, respectively. RESULTS: Genistein (40 μmol·L-1) significantly suppressed the growth of NB4 cells, while a large amount of cells died with the prolongation of the drug exposure time. At concentration larger than 40 μmol·L-1, genistein induced condensation of chromatin, breakage of nucleus, and appearance of DNA ladder after agarose electrophoresis in NB4 cells. In consistent with the induction of apoptosis, genistein inhibited expression of bcl-2 gene. At 10 ∼ 200 μmol·L-1, genistein stimulated the topoisomerase II-mediated DNA breakage. On the other hand, genistein induced increase of NBT positive cell number, but the positive rates were lower than 50%. CONCLUSION: Genistein inhibited the growth of NB4 cells through induction of apoptosis and cell death. The mechanism of action might be associated with suppression of DNA topoisomerase II activity. Induction of differentiation may contribute little to the therapeutic activities of genistein in leukemia cells.

AB - AIM: To investigate the possible actions of isoflavone genistein in inducing apoptosis and differentiation of NB4 leukemia cells. METHODS: NBT dye reduction ability was used as the biomarker of differentiation of NB4 cells. Apoptosis was assayed through genomic DNA gel electrophoresis. Expression of bcl-2 gene and DNA topoisomerase II activity were examined with Northern blot analysis and plasmid DNA breakage analysis, respectively. RESULTS: Genistein (40 μmol·L-1) significantly suppressed the growth of NB4 cells, while a large amount of cells died with the prolongation of the drug exposure time. At concentration larger than 40 μmol·L-1, genistein induced condensation of chromatin, breakage of nucleus, and appearance of DNA ladder after agarose electrophoresis in NB4 cells. In consistent with the induction of apoptosis, genistein inhibited expression of bcl-2 gene. At 10 ∼ 200 μmol·L-1, genistein stimulated the topoisomerase II-mediated DNA breakage. On the other hand, genistein induced increase of NBT positive cell number, but the positive rates were lower than 50%. CONCLUSION: Genistein inhibited the growth of NB4 cells through induction of apoptosis and cell death. The mechanism of action might be associated with suppression of DNA topoisomerase II activity. Induction of differentiation may contribute little to the therapeutic activities of genistein in leukemia cells.

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