Document Detail

3-O-methylfunicone, a secondary metabolite produced by Penicillium pinophilum, induces growth arrest and apoptosis in HeLa cells.
MedLine Citation:
PMID:  15548174     Owner:  NLM     Status:  MEDLINE    
3-O-Methylfunicone (OMF) is a secondary metabolite produced by the soil fungus Penicillium pinophilum which has cytostatic properties. The aim of this study was to investigate the mechanisms by which such properties are exerted, with special reference to any anti-proliferative and apoptotic potential, on HeLa cells. OMF treatment caused about 44% inhibition of cell growth after 24 h, and modifications in the tubulin fibre organization. In addition, a significant increase in p21 mRNA expression and a decrease in cyclin D1 and Cdk4 mRNA expression resulted at the same time. Apoptosis induction was demonstrated by the annexin V assay, cytofluorimetric analysis of the DNA content of the sub-G1 fraction and DNA laddering. Taken together, our data showed that the compound inhibits proliferation of HeLa cells by several mechanisms, such as disruption of tubulin fibres, cell cycle arrest and apoptosis induction. The capacity of the compound to affect the cell cycle and to modulate apoptosis is indicative of a potential for the development of a new agent for cancer chemotherapy.
E Buommino; R Nicoletti; G M Gaeta; M Orlando; M L Ciavatta; A Baroni; M A Tufano
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell proliferation     Volume:  37     ISSN:  0960-7722     ISO Abbreviation:  Cell Prolif.     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-11-19     Completed Date:  2005-01-11     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  9105195     Medline TA:  Cell Prolif     Country:  England    
Other Details:
Languages:  eng     Pagination:  413-26     Citation Subset:  IM    
Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Second University of Naples, Italy.
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MeSH Terms
Annexin A5 / metabolism
Antineoplastic Agents / toxicity
Apoptosis / drug effects,  physiology
Cell Cycle / drug effects,  physiology
Cell Cycle Proteins / genetics
Cell Division / drug effects,  physiology
Cyclin D1 / genetics
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinases / genetics
Cytotoxins / toxicity*
DNA Fragmentation / drug effects,  physiology
Drug Screening Assays, Antitumor
Growth Inhibitors / toxicity*
HeLa Cells
Microtubules / drug effects,  metabolism
Molecular Structure
Penicillium / metabolism*
Proto-Oncogene Proteins / genetics
Pyrones / toxicity*
RNA, Messenger / drug effects,  metabolism
Tubulin / drug effects,  metabolism
Reg. No./Substance:
0/3-O-methylfunicone; 0/Annexin A5; 0/Antineoplastic Agents; 0/CDKN1A protein, human; 0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cytotoxins; 0/Growth Inhibitors; 0/Proto-Oncogene Proteins; 0/Pyrones; 0/RNA, Messenger; 0/Tubulin; 136601-57-5/Cyclin D1; EC protein, human; EC Kinase 4; EC Kinases

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