Document Detail


The mechanism of ellipticine-induced apoptosis and cell cycle arrest in human breast MCF-7 cancer cells.
MedLine Citation:
PMID:  15896464     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ellipticine, a cytotoxic plant alkaloid, is known to inhibit topoisomerase II. Here, we first report the molecular mechanism of ellipticine's apoptotic action in human breast MCF-7 cancer cells. Treatment of cells with ellipticine resulted in inhibition of growth, and G2/M phase arrest of the cell cycle. This effect was associated with a marked increase in the protein expression of p53 and, p21/WAF1 and KIP1/p27, but not of WAF1/p21. Ellipticine treatment increased the expression of Fas/APO-1 and its ligands, mFas ligand and sFas ligand, and subsequent activation of caspase-8. The mitochondrial apoptotic pathway amplified the Fas/Fas ligand death receptor pathway by Bid interaction. This effect was found to result in a significant increase in activation of caspase-9. Taken together, we have concluded that the molecular mechanisms during ellipticine-mediated growth inhibition and induction of apoptosis in MCF-7 cells were due to (1) cell cycle arrest and induction of apoptosis, (2) induction of p53 and KIP1/p27 expression, (3) triggering of Fas/Fas ligand pathway, (4) disruption of mitochondrial function, and (5) the apoptotic signaling was amplified by cross-talk between Fas death receptor and mitochondrial apoptotic pathway.
Authors:
Po-Lin Kuo; Ya-Ling Hsu; Cheng-Hsiung Chang; Chun-Ching Lin
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Publication Detail:
Type:  Journal Article     Date:  2004-11-11
Journal Detail:
Title:  Cancer letters     Volume:  223     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-05-17     Completed Date:  2005-07-21     Revised Date:  2014-07-21    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  293-301     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Breast Neoplasms / pathology*
Carrier Proteins / biosynthesis*
Cell Cycle / drug effects*
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p27
Ellipticines / pharmacology*
Fas Ligand Protein
Female
Gene Expression Regulation
Humans
Intracellular Signaling Peptides and Proteins
Membrane Glycoproteins
Mitochondria
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / biosynthesis*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/CDKN1B protein, human; 0/Carrier Proteins; 0/Ellipticines; 0/FASLG protein, human; 0/Fas Ligand Protein; 0/Intracellular Signaling Peptides and Proteins; 0/Membrane Glycoproteins; 0/Tumor Suppressor Protein p53; 117VLW7484/ellipticine; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27
Comments/Corrections
Erratum In:
Cancer Lett. 2014 Jul 28;349(2):154

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