title: Cell-growth and migration inhibition of human mesothelioma cells induced by 3-O-methylfunicone from Penicillium pinophilum and cisplatin.
abstract: Malignant pleural mesothelioma is a fatal malignancy linked to asbestos exposure. The main challenge for mesothelioma treatment is to go beyond the drug resistance, in particular against cisplatin (CDDP), one of the most used chemotherapeutic drug. 3-O-methylfunicone (OMF) is a metabolite produced by the fungus Penicillium pinophilum; its antiproliferative properties have been previously studied in vitro. Particularly, OMF is able to inhibit mesothelioma cell motility. To improve the effects of CDDP by-passing the resistance of mesothelioma cells to this drug, in the present study we investigated the combined treatment of OMF with CDDP respectively in an established mesothelioma cell line (NCI) and primary mesothelioma cells (Mest). As compared to the effect of single treatments, the combination of OMF and CDDP resulted in a stronger inhibition of NCI and Mest cell proliferation. OMF combination with CDDP was also able to affect the migratory ability of NCI and Mest cells by down-regulating αv and β5 expression and reducing metalloproteinase 2 (MMP-2) production. In addition, this association was effective in modulating VEGF gene expression. This finding highlights the possibility to use OMF and CDDP together to regulate angiogenesis and tumour progression in mesothelioma.
authors.affiliation: Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Second University of Naples, via Luigi de Crecchio n°7, 80128 Naples, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Buommino
authors.forename: Anna
authors.initials: A
authors.lastname: De Filippis
authors.forename: Rosario
authors.initials: R
authors.lastname: Nicoletti
authors.forename: Massimo
authors.initials: M
authors.lastname: Menegozzo
authors.forename: Simona
authors.initials: S
authors.lastname: Menegozzo
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Ciavatta
authors.forename: Antonietta
authors.initials: A
authors.lastname: Rizzo
authors.forename: Virginia
authors.initials: V
authors.lastname: Brancato
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Tufano
authors.forename: Giovanna
authors.initials: G
authors.lastname: Donnarumma
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D008654:Mesothelioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D010407:Penicillium / Q000737:chemistry*; D011753:Pyrones / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C450900:3-O-methylfunicone; D011753:Pyrones; D012333:RNA, Messenger; D019030:Receptors, Vitronectin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C064660:integrin alphaVbeta5; D020778:Matrix Metalloproteinase 2; D002945:Cisplatin