Document Detail

Differential involvement of mitochondria during ursolic acid-induced apoptotic process in HaCaT and M4Beu cells.
MedLine Citation:
PMID:  18097588     Owner:  NLM     Status:  MEDLINE    
Ursolic acid (UA) is a pentacyclic triterpenoid compound which exists widely in nature and is known to have a pleitropic biological activity profile. For the last few decades, extensive work has been carried out to establish its biological activities and pharmacological actions. It is described as a promising chemopreventive agent with an antiproliferative effect on cancer cells that stems from its ability to induce apoptosis. We investigated and compared the role played by mitochondria during the apoptotic process induced by UA in human HaCaT-derived keratinotic cells and M4Beu human melanoma cells. In both cell lines, UA induced significant caspase-3 activation, the downstream central effector of apoptosis. Subsequent JC-1/TOTO-3 double staining clearly demonstrated that UA induces strong mitochondrial-transmembrane potential collapse in M4Beu cells, while mitochondria from HaCaT-treated cells remain largely unstimulated. This was confirmed by Western blot analysis, which revealed a Bax/Bcl-2-balance change in favor of Bax, the proapoptotic member, in UA-treated M4Beu cells. It can be concluded that UA induces apoptosis in M4Beu through the mitochondrial pathway, while other mechanisms are activated in the case of HaCaT cells.
Raphaël Emmanuel Duval; Pierre-Olivier Harmand; Chantal Jayat-Vignoles; Jeanne Cook-Moreau; Aline Pinon; Christiane Delage; Alain Simon
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Oncology reports     Volume:  19     ISSN:  1021-335X     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2007-12-21     Completed Date:  2008-02-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  145-9     Citation Subset:  IM    
EA 4021, Laboratoire de Chimie-Physique, Faculté de Pharmacie, 87025 Limoges Cedex, France.
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MeSH Terms
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects*
Blotting, Western
Caspase 3 / drug effects,  metabolism
Caspase 9 / drug effects,  metabolism
Cell Line, Tumor
Flow Cytometry
Keratinocytes / drug effects,  metabolism
Melanoma / metabolism
Membrane Potential, Mitochondrial / drug effects
Mitochondria / drug effects*
Proto-Oncogene Proteins c-bcl-2 / drug effects,  metabolism
Triterpenes / pharmacology*
bcl-2-Associated X Protein / drug effects,  metabolism
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Proto-Oncogene Proteins c-bcl-2; 0/Triterpenes; 0/bcl-2-Associated X Protein; 77-52-1/ursolic acid; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 9

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