title: 3-O-methylfunicone produced by penicillium pinophilum affects cell motility of breast cancer cells, downregulating alphavbeta5 integrin and inhibiting metalloproteinase-9 secretion.
abstract: 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.
authors.affiliation: Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, SUN, Naples, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Buommino
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Boccellino
authors.forename: Anna
authors.initials: A
authors.lastname: De Filippis
authors.forename: Marcella
authors.initials: M
authors.lastname: Petrazzuolo
authors.forename: Valentina
authors.initials: V
authors.lastname: Cozza
authors.forename: Rosario
authors.initials: R
authors.lastname: Nicoletti
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Ciavatta
authors.forename: Lucio
authors.initials: L
authors.lastname: Quagliuolo
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Tufano
mesh_terms: 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
chemical_list: C450900:3-O-methylfunicone; D016023:Integrins; D011753:Pyrones; D019030:Receptors, Vitronectin; D014404:Tubulin; C064660:integrin alphaVbeta5; D005337:Fibrin; D020780:Matrix Metalloproteinase 9