Top

Published in:

01-08-2012 | PRECLINICAL STUDIES

Cell-growth and migration inhibition of human mesothelioma cells induced by 3-O-Methylfunicone from Penicillium pinophilum and cisplatin

Authors: Elisabetta Buommino, Anna De Filippis, Rosario Nicoletti, Massimo Menegozzo, Simona Menegozzo, Maria Letizia Ciavatta, Antonietta Rizzo, Virginia Brancato, Maria Antonietta Tufano, Giovanna Donnarumma

Published in: Investigational New Drugs | Issue 4/2012

Summary

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.

Lee AY et al (2007) Update on the molecular biology of malignant mesothelioma. Cancer 109:1454–1461CrossRefPubMed

Fennell DA et al (2008) Advances in system therapy of malignant mesothelioma. Nat Clin Pract Oncol 5:136–147CrossRefPubMed

Vogelzang NJ et al (2003) Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 21:2636–2644CrossRefPubMed

Montopoli M et al (2009) Cell-cycle inhibition and apoptosis induced by curcumin and cisplatin or oxaliplatin in human ovarian carcinoma cells. Cell Prolif 42:195–206CrossRefPubMed

Newman DJ, Cragg G, Snader KM (2003) Natural products as sources of new drugs over the period 1981–2002. J Nat Prod 66:1022–1037CrossRefPubMed

Nicoletti R, Ciavatta L, Buommino E, Tufano MA (2008) Antitumor extrolites produced by Penicillium species. Int J Biomed Pharm Sci 2:1–23

De Stefano S, Nicoletti R, Milone A, Zambardino S (1999) 3-O-Methylfunicone, a fungitoxic metabolite produced by the fungus Penicillium pinophilum. Phytochemistry 52:1399–1401CrossRef

Nicoletti R, De Stefano M, De Stefano S, Trincone A, Marziano F (2004) Identification of fungitoxic metabolites produced by some Penicillium isolates antagonistic to Rhizoctonia solani. Mycopathologia 158:465–474CrossRefPubMed

Buommino E, Nicoletti R, Gaeta GM, Orlando M, Ciavatta ML, Baroni A et al (2004) 3-O-methylfunicone, a secondary metabolite produced by Penicillium pinophilum, induces growth arrest and apoptosis in HeLa cells. Cell Prolif 37:413–426CrossRefPubMed

10.

Buommino E, Boccellino M, De Filippis A, Cozza V, Nicoletti R, Ciavatta ML et al (2007) 3-O-methylfunicone by Penicillium pinophilum affects cell motility of breast cancer cells, down-regulating αVβ5 integrin and inhibiting MMP9 secretion. Mol Carcinog 46:930–940CrossRefPubMed

11.

Baroni A, De Luca A, De Filippis A, Petrazzuolo M, Manente L, Nicoletti R et al (2009) 3-O-methylfunicone, a metabolite from Penicillium pinophilum, inhibits proliferation of human melanoma cells by causing G₂/M arrest and inducing apoptosis. Cell Prolif 42:541–553CrossRefPubMed

12.

Buommino E, Paoletti I, De Filippis A, Nicoletti R, Ciavatta ML, Menegozzo S, Menegozzo M, Tufano MA (2010) 3-O-Methylfunicone, a metabolite produced by Penicillium pinophilum, modulates ERK1/2 activity, affecting cell motility of human mesothelioma cells. Cell Prolif 43:114–123CrossRefPubMed

13.

Foster MR, Johnson JE, Olson SJ, Allred DC (2001) Immunohistochemical analysis of nuclear versus cytoplasmic staining of WT1 in malignant mesotheliomas and primary pulmonary adenocarcinomas. Arch Pathol Lab Med 125:1316–1320PubMed

14.

Szczepulska-Wojcik E, Langfort R, Roszkowski-Aliz K (2007) A comparative evaluation of immunohistochemical markers for the differential diagnosis between malignant mesothelioma, non-small cell carcinoma involving the pleura, and benign reactive mesothelial cellproliferation. Pneumonol Alergol Pol 75:57–69PubMed

15.

Woods D, Cherwinski H, Venetsanakos E, Bhat A, Gysin S, Humbert M et al (2001) Induction of b3-integrin gene expression by sustained activation of the Ras-regulated Raf-MEK-Extracellular signal-regulated kinase signaling pathway. Mol Cell Biol 21:3192–3205CrossRefPubMed

16.

Lee YJ, Cho HN, Soh JW, Jhon GJ, Cho CK, Chung HY, Bae S, Lee SJ, Lee YS (2003) Oxidative stress-induced apoptosis is mediated by ERK1/2 phosphorylation. Exp Cell Res 291:251–266CrossRefPubMed

17.

Peto J, Decarli A, La Vecchia C et al (1999) The European mesothelioma epidemic. Br J Cancer 86:1970–1971

18.

Le GV, Takahashi K, Karjalainen A, Delgermaa V, Hoshuyama T, Miyamura Y, Furuya S, Higashi T, Pan G, Wagner G (2010) National use of asbestos in relation to economic development. Environ Health Perspect 118:116–119PubMed

19.

Toyooka S, Kishimoto T, Date H (2008) Advances in the molecular biology of malignant mesothelioma. Acta Med Okayama 62:1–7PubMed

20.

Bertolini F, Paul S, Mancuso P, Monestiroli S, Gobbi A, Shaked Y, Kerbel RS (2003) Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells. Canc Res 63:4342–4346

21.

Damber JE, Vallbo C, Albertsson P, Lennernäs B, Norrby K (2006) The anti-tumour effect of low-dose continuous chemotherapy may partly be mediated by thrombospondin. Cancer Chemother Pharmacol 58:354–360CrossRefPubMed

22.

Fusco V, Ardizzoni A, Merlo F, Cinquegrana A, Faravelli B, De Palma M, Chessa L, Nicolò G, Serra M, Capaccio A et al (1993) Malignant pleural mesothelioma. Multivariate analysis of prognostic factors on 113 patients. Anticancer Res 13:683–689PubMed

23.

Elbahaie AM, Kamel DE, Lawrence J, Davidson NG (2009) Late cutaneous metastases to the face from malignant pleural mesothelioma: a case report and review of the literature. World J Surg Oncol 7:84CrossRefPubMed

24.

Demiroglu-Zergeroglu A, Basara-Cigerim B, Kilic E, Yanikkaya-Demirel G (2010) The investigation of effects of Quercetin and its combination with cisplatin on malignant mesothelioma cells in vitro. J Biomed Biotechnol 2010:851589CrossRefPubMed

25.

Liu Z, Ivanoff A, Klominek J (2001) Expression and activity of matrix metalloproteases in human malignant mesothelioma cell lines. Int J Cancer 91:638–643CrossRefPubMed

26.

Strizzi L, Catalano A, Vianale G, Orecchia S, Casalini A, Tassi G, Puntoni R, Mutti L, Procopio A (2001) Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma. J Pathol 193:468–475CrossRefPubMed

Title: Cell-growth and migration inhibition of human mesothelioma cells induced by 3-O-Methylfunicone from Penicillium pinophilum and cisplatin
Authors: Elisabetta Buommino
Anna De Filippis
Rosario Nicoletti
Massimo Menegozzo
Simona Menegozzo
Maria Letizia Ciavatta
Antonietta Rizzo
Virginia Brancato
Maria Antonietta Tufano
Giovanna Donnarumma
Publication date: 01-08-2012
Publisher: Springer US
Published in: Investigational New Drugs / Issue 4/2012
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-011-9698-1

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Summary

Please log in to get access to this content

Other articles of this Issue 4/2012

First-line metronomic chemotherapy in a metastatic model of spontaneous canine tumours: a pilot study

Sequential therapy with sunitinib and sorafenib in metastatic hepatocellular carcinoma

Phase I and pharmacokinetic study of capecitabine and the oral mTOR inhibitor everolimus in patients with advanced solid malignancies

Biological evaluation of MR36, a novel non-polyglutamatable thymidylate synthase inhibitor that blocks cell cycle progression in melanoma cell lines

Quaternary ammonium-melphalan conjugate for anticancer therapy of chondrosarcoma: in vitro and in vivo preclinical studies

Borrelidin, a small molecule nitrile-containing macrolide inhibitor of threonyl-tRNA synthetase, is a potent inducer of apoptosis in acute lymphoblastic leukemia

Keynote webinar | Spotlight on antibody–drug conjugates in cancer