Magnolol induces apoptosis in human leukemia cells via cytochrome c release and caspase activation

Wen Bin Zhong, Chih Yuan Wang, Kuo Jang Ho, Fung Jou Lu, Tien Chun Chang, Wen Sen Lee

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Magnolol, isolated from the stem bark of Magnolia officnalis, was found to inhibit proliferation of human HL-60 cells and Jurkat T leukemia cells via inducing apoptosis in a dose- and time-dependent manner. By contrast, magnolol did not cause apoptosis in neutrophils and peripheral blood mononuclear cells of healthy donors. Apoptosis was determined by detection of DNA fragmentation in gel electrophoresis, morphological alternations by flow cytometry, quantification of phosphatidylserine externalization by Annexin V labeling and oligonucleosomal DNA content by TUNEL labeling. Activation of caspase-9, -3 and -2, and the proteolytic cleavage of poly(ADP-ribose) polymerase were found during apoptosis induced by magnolol. In addition, both pan-caspase and selective caspase-9 inhibitor blocked magnolol-induced apoptosis. The apoptosis could also be partially attenuated by caspase-3 and -2 inhibitors. Magnolol induced the reduction of mitochondrial transmembrane potential and the release of cytochrome c into cytoplasm. In conclusion, our findings indicate that magnolol-induced apoptotic signaling is carried out through mitochondria alternations to caspase-9 and that then the downstream effector caspases are activated sequentially. Magnolol could be a potentially effective drug for leukemia with low toxicity to Anti-normal blood cells and it merits further investigation.

Original languageEnglish
Pages (from-to)211-217
Number of pages7
JournalAnti-Cancer Drugs
Volume14
Issue number3
DOIs
Publication statusPublished - Mar 2003
Externally publishedYes

Fingerprint

Caspases
Cytochromes c
Leukemia
Apoptosis
Caspase 9
Caspase 3
Blood Cells
Magnolia
Effector Caspases
Caspase 2
T-Cell Leukemia
Caspase Inhibitors
Poly(ADP-ribose) Polymerases
HL-60 Cells
Annexin A5
Phosphatidylserines
In Situ Nick-End Labeling
DNA Fragmentation
magnolol
Membrane Potentials

Keywords

  • Apoptosis
  • Caspase
  • Cytochrome c
  • Leukemia
  • Magnolol

ASJC Scopus subject areas

  • Pharmacology
  • Cancer Research
  • Oncology

Cite this

Magnolol induces apoptosis in human leukemia cells via cytochrome c release and caspase activation. / Zhong, Wen Bin; Wang, Chih Yuan; Ho, Kuo Jang; Lu, Fung Jou; Chang, Tien Chun; Lee, Wen Sen.

In: Anti-Cancer Drugs, Vol. 14, No. 3, 03.2003, p. 211-217.

Research output: Contribution to journalArticle

Zhong, Wen Bin ; Wang, Chih Yuan ; Ho, Kuo Jang ; Lu, Fung Jou ; Chang, Tien Chun ; Lee, Wen Sen. / Magnolol induces apoptosis in human leukemia cells via cytochrome c release and caspase activation. In: Anti-Cancer Drugs. 2003 ; Vol. 14, No. 3. pp. 211-217.
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