Document Detail


Induction of apoptosis in human lung carcinoma cells by the water extract of Panax notoginseng is associated with the activation of caspase-3 through downregulation of Akt.
MedLine Citation:
PMID:  19513559     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The root of Panax notoginseng is highly valued and commonly used in Oriental medicine. Although recent experimental data have revealed the proapoptotic potency of P. notoginseng extracts, the underlying molecular mechanisms of this apoptotic activity have not yet been studied in detail. In the present study, the effects of the water extract of P. notoginseng (WEPN) on the growth of human lung carcinoma cells were investigated. It was found that the exposure of A549 and NIC-H460 cells to WEPN resulted in growth inhibition and the induction of apoptosis in a dose-dependent manner. The WEPN treatment induced the upregulation of pro-apoptotic Bax, downregulation of anti-apoptotic Bcl-2 expression and loss of mitochondrial membrane potential (MMP), which was associated with the proteolytic activation of caspases and the concomitant degradation of poly(ADP ribose) polymerase (PARP) protein. However, the caspase-3-specific inhibitor z-DEVD-fmk blocked PARP degradation and increased the survival rate of WEPN-treated cells. Moreover, the activity of Akt was downregulated in WEPN-treated cells and the phosphatidylinositol-3 kinase (PI3K)/Akt inhibitor LY294002 sensitized the cells to WEPN-induced apoptosis through enhancing the activation of caspase-3 and loss of MMP. The results indicated that the major regulators of WEPN-induced apoptosis in human lung carcinoma cells are the Bcl-2 family and caspase-3, which are associated with mitochondrial dysfunction and dephosphorylation of the Akt signaling pathway.
Authors:
Seung Chan Park; Hwa Seung Yoo; Cheol Park; Chong Kwan Cho; Gi-Young Kim; Wun-Jae Kim; Yeon-Weol Lee; Yung Hyun Choi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of oncology     Volume:  35     ISSN:  1019-6439     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-10     Completed Date:  2009-08-06     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  121-7     Citation Subset:  IM    
Affiliation:
Department of East-West Cancer Center, College of Oriental Medicine, Daejeon University, Daejeon 301-724, Korea.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects*
Caspase 3 / metabolism*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Chromones / pharmacology
Cysteine Proteinase Inhibitors / pharmacology
Dose-Response Relationship, Drug
Down-Regulation
Drugs, Chinese Herbal / pharmacology*
Enzyme Activation
Humans
Lung Neoplasms / enzymology*,  pathology*
Membrane Potential, Mitochondrial / drug effects
Mitochondria / drug effects,  enzymology
Morpholines / pharmacology
Oligopeptides / pharmacology
Phosphorylation
Poly(ADP-ribose) Polymerases / metabolism
Protein Kinase Inhibitors / pharmacology
Proto-Oncogene Proteins c-akt / metabolism*
Proto-Oncogene Proteins c-bcl-2 / metabolism
Signal Transduction / drug effects*
bcl-2-Associated X Protein / metabolism
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/BAX protein, human; 0/Chromones; 0/Cysteine Proteinase Inhibitors; 0/Drugs, Chinese Herbal; 0/Morpholines; 0/Oligopeptides; 0/Panax notoginseng extract; 0/Protein Kinase Inhibitors; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2-Associated X Protein; 0/benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3

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