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Effector mechanism of magnolol‐induced apoptosis in human lung squamous carcinoma CH27 cells
Author(s) -
Yang ShuEr,
Hsieh MingTsuen,
Tsai TungHu,
Hsu ShihLan
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705024
Subject(s) - magnolol , magnolia officinalis , apoptosis , cytochrome c , caspase , honokiol , microbiology and biotechnology , caspase 3 , biology , programmed cell death , intrinsic apoptosis , mapk/erk pathway , bcl 2 associated x protein , chemistry , signal transduction , pharmacology , biochemistry , medicine , pathology , alternative medicine , traditional chinese medicine
Magnolol, an active component isolated from the root and stem bark of Magnolia officinalis , has been reported to exhibit antitumour effects, but little is known about its molecular mechanisms of action. Magnolol inhibited proliferation of human lung squamous carcinoma CH27 cells at low concentrations (10–40 μ M ), and induced apoptosis at high concentrations (80–100 μ M ). Treatment with 80 μ M magnolol significantly increased the expression of Bad and Bcl‐X S proteins, whereas it decreased the expression of Bcl‐X L . Overexpression of Bcl‐2 protected CH27 cells against magnolol‐triggered apoptosis. Magnolol treatment resulted in accumulation of cytosolic cytochrome c and activation of caspase‐9 and downstream caspases (caspase‐3 and ‐6). Pretreatment with z‐VAD‐fmk markedly inhibited magnolol‐induced cell death, but did not prevent cytosolic cytochrome c accumulation. Magnolol induced a modest and persistent JNK activation and ERK inactivation in CH27 cells without evident changes in the protein levels. The responsiveness of JNK and ERK to magnolol suggests the involvement of these kinases in the initiation of the apoptosis process. These results indicate that regulation of the Bcl‐2 family, accumulation of cytosolic cytochrome c , and activation of caspase‐9 and caspase‐3 may be the effector mechanisms of magnolol‐induced apoptosis.British Journal of Pharmacology (2003) 138 , 193–201. doi: 10.1038/sj.bjp.0705024