3-O-methylfunicone produced by penicillium pinophilum affects cell motility of breast cancer cells, downregulating alphavbeta5 integrin and inhibiting metalloproteinase-9 secretion.
Recent evidence assigns integrins and metalloproteinases (MMPs) an important role in regulating tumor cell progression. Here, we demonstrate that 3-O-methylfunicone (OMF), a secondary metabolite produced by Penicillium pinophilum, affects cell proliferation and motility of breast cancer MCF-7 cells, downregulating alphavbeta5 integrin, and inhibiting MMP-9 secretion. This effect was absent when the non-tumoral MCF-10 cell line was used. Inhibition of cell motility was also associated to modifications in cell shape and in the distribution of tubulin fibers of OMF-treated MCF-7 cells. In addition, a possible effect on survivin and hTERT was also investigated. We found that OMF strongly inhibits survivin and hTERT gene expression. The results of this study indicate that OMF-induced inhibition of cell motility may be mediated through the modulation of alphavbeta5 integrin and MMP-9 secretion. In addition, the inhibition of typical markers of tumor progression such as hTERT and survivin in MCF-7 and their inactivity towards MCF10 provide strong evidence for a potential use of OMF in anticancer therapy.
Buommino
Elisabetta
E
Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, SUN, Naples, Italy.
Boccellino
Mariarosaria
M
De Filippis
Anna
A
Petrazzuolo
Marcella
M
Cozza
Valentina
V
Nicoletti
Rosario
R
Ciavatta
Maria Letizia
ML
Quagliuolo
Lucio
L
Tufano
Maria Antonietta
MA
D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D015536:Down-Regulation; D004341:Drug Evaluation; D005260:Female; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D010407:Penicillium / Q000378:metabolism; D011753:Pyrones / Q000737:chemistry / Q000494:pharmacology*; D019030:Receptors, Vitronectin / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
C450900:3-O-methylfunicone; D016023:Integrins; D011753:Pyrones; D019030:Receptors, Vitronectin; D014404:Tubulin; C064660:integrin alphaVbeta5; D005337:Fibrin; D020780:Matrix Metalloproteinase 9