Document Detail


Sanguinarine cytotoxicity on mouse melanoma K1735-M2 cells--nuclear vs. mitochondrial effects.
MedLine Citation:
PMID:  18692024     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Sanguinarine (SANG) is an alkaloid recognized to have anti-proliferative activity against various human tumour cell lines. No data is available on the susceptibility of advanced malignant melanoma to SANG, although this disease has a very poor prognosis if not detected in time due to the resistance to conventional chemotherapy. The present work was designed to study the nuclear and mitochondrial involvement in the pro-apoptotic effect of SANG in an invasive mouse melanoma cell line. The results obtained show that SANG is primarily accumulated by the cell nuclei, causing inhibition of cell proliferation and inducing cell death, as confirmed by an increase in sub-G1 peaks. At low concentrations, SANG induces mitochondrial depolarization in a sub-population of melanoma cells, which also generally displayed strong nuclear labelling of phosphorylated histone H2AX. Western blotting revealed an increase in p53, but not Bax protein, in both whole-cell extracts and in mitochondrial fractions. Isolated hepatic mitochondrial fractions revealed that SANG affects the mitochondrial respiratory chain, and has dual effects on mitochondrial calcium loading capacity. We suggest that SANG is able to induce apoptosis in metastatic melanoma cells. The knowledge of mitochondrial vs. nuclear effects of SANG is important in the development of this promising compound for clinical use against aggressive melanoma.
Authors:
Teresa L Serafim; Júlio A C Matos; Vilma A Sardão; Gonçalo C Pereira; Ana F Branco; Sandro L Pereira; Donna Parke; Edward L Perkins; António J M Moreno; Jon Holy; Paulo J Oliveira
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-19
Journal Detail:
Title:  Biochemical pharmacology     Volume:  76     ISSN:  1873-2968     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-11-21     Completed Date:  2009-01-09     Revised Date:  2009-05-21    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1459-75     Citation Subset:  IM    
Affiliation:
Center for Neurosciences and Cell Biology, Department of Zoology, University of Coimbra, P-3004-517 Coimbra, Portugal.
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MeSH Terms
Descriptor/Qualifier:
Animals
Benzophenanthridines / pharmacology*
Blotting, Western
Cell Line, Tumor
Cell Nucleus / drug effects*
Cell Proliferation
Drug Screening Assays, Antitumor
Histones / metabolism
Isoquinolines / pharmacology*
Melanoma, Experimental / metabolism,  pathology*,  ultrastructure
Mice
Mitochondria / drug effects*
Phosphorylation
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/Benzophenanthridines; 0/Histones; 0/Isoquinolines; 2447-54-3/sanguinarine

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