3-O-Methylfunicone, a metabolite produced by Penicillium pinophilum, modulates ERK1/2 activity, affecting cell motility of human mesothelioma cells.
OBJECTIVE
3-O-methylfunicone (OMF), a secondary metabolite produced by Penicillium pinophilum, affects cell proliferation and motility in a variety of human solid tumours. The aim of this study was to demonstrate whether OMF has the ability to arrest cell division and motility, in a human mesothelioma cell line. Malignant mesothelioma is an aggressive cancer that does not respond to standard therapies the cells of which are considered to be highly resistant to apoptosis.


METHODS
Cell motility and invasion were measured using a modified Boyden chamber. Gene expression was examined by RT-PCR, while ERK1/2 was investigated by Western blot analysis. All experiments were also performed on primary cultures of mesothelial cells.


RESULTS
The present study shows that OMF inhibited motility of the NCI mesothelioma cell line by modulating ERK signalling activity, and affected alphaVbeta5 integrin and MMP-2 expression, inducing marked downregulation at both mRNA and protein levels. Substantial downregulation of VEGF gene expression was also demonstrated. These effects were not observed in normal mesothelial cell cultures.


CONCLUSIONS
OMF may have potential as a naturally derived anti-tumour drug for treatment of mesothelioma.
Buommino
E
E
Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, SUN, Naples, Italy.
Paoletti
I
I
De Filippis
A
A
Nicoletti
R
R
Ciavatta
M L
ML
Menegozzo
S
S
Menegozzo
M
M
Tufano
M A
MA
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D015536:Down-Regulation; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010407:Penicillium / Q000378:metabolism; D011753:Pyrones / Q000494:pharmacology*; D019030:Receptors, Vitronectin / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
C450900:3-O-methylfunicone; D011753:Pyrones; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020778:Matrix Metalloproteinase 2
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