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

Our plain-English summary of Cell-growth and migration inhibition of human mesothelioma cells induced by 3-O-methylfunicone from Penicillium pinophilum and cisplatin, by E. Buommino, A. De Filippis, R. Nicoletti, et al (Investigational New Drugs, 2012).

The study

• Authors: E. Buommino, A. De Filippis, R. Nicoletti, M. Menegozzo, S. Menegozzo, M.L. Ciavatta, A. Rizzo, V. Brancato, M.A. Tufano, G. Donnarumma
• Journal: Investigational New Drugs
• Published: 2012;30(4):1343-51
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

This was a laboratory study of human mesothelioma cells grown in dishes. It did not study asbestos exposure and did not involve patients being treated. The authors tested 3-O-methylfunicone (OMF), a substance made by the fungus Penicillium pinophilum, alone and together with the chemotherapy drug cisplatin. They used an established mesothelioma cell line (NCI) and primary cells (Mest) grown from pleural biopsies of one patient with malignant pleural mesothelioma. After 48 hours, OMF at 30 micrograms per millilitre plus cisplatin at 1.25 micrograms per millilitre reduced proliferation by about 73% in NCI cells and by 90% in Mest cells. The article reports that OMF alone reduced it by 55% and 26% respectively. The combination reduced cell migration by 83% in both cell types. OMF alone reduced migration by about 59% (NCI) and 62% (Mest), and cisplatin alone by about 57% and 70%. The combination also lowered the activity of genes for the αV and β5 integrins, MMP-2 and VEGF, which are involved in cell movement and blood-vessel growth. The authors concluded that the two compounds acted synergistically.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell-culture experiment
• Who was studied: Human mesothelioma cells: the established cell line NCI-H2452 (NCI), and primary mesothelioma cells (Mest) grown from pleural biopsies of one patient confirmed as having malignant pleural mesothelioma. Each experiment was performed at least three times.
• Exposure: Not an asbestos exposure. Cells were treated with 3-O-methylfunicone (OMF) and/or cisplatin (CDDP). The combination experiments used OMF at 30 μg/ml and CDDP at 0.75 or 1.25 μg/ml for 48 h. Dose-finding used OMF at 25, 50 and 100 μg/ml and CDDP from 0.75 to 15 μg/ml.
• Main results:
  • OMF alone at 25 μg/ml for 48 h inhibited proliferation by 46% in NCI cells and 26% in Mest cells, compared with untreated controls.
  • OMF alone at 50 and 100 μg/ml for 48 h reduced proliferation by 63% and 80% in NCI cells, and by 61% and 76% in Mest cells.
  • Cisplatin alone at 15 μg/ml produced the strongest inhibition, reducing proliferation by about 97% in NCI cells and 92% in Mest cells.
  • In NCI cells, OMF 30 μg/ml plus CDDP 0.75 μg/ml reduced proliferation by about 45%, and OMF 30 μg/ml plus CDDP 1.25 μg/ml by about 73%. OMF alone reduced it by 55%.
  • In Mest cells, the same two combinations reduced proliferation by 79% and 90%. The article reports that OMF alone reduced it by 26%.
  • In NCI and Mest cells, combined OMF 30 μg/ml and CDDP 1.25 μg/ml lowered expression of the αV and β5 integrin genes more strongly than either treatment alone.
  • The combination strongly decreased MMP-2 gene expression after 48 h; OMF or CDDP alone did not produce the same effect.
  • The combination produced a strong decrease in VEGF gene expression.
  • Migration fell by about 59% in NCI cells and 62% in Mest cells with OMF alone, and by about 57% and 70% with CDDP alone.
  • Combined OMF and cisplatin reduced migration by 83% in both NCI and Mest cells, which the authors called an additive inhibitory effect.
• The authors' conclusion: The authors concluded that this was the first study of OMF combined with cisplatin. They wrote that the two acted synergistically to inhibit tumour cell motility and the processes of new blood-vessel formation.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Cisplatin, Pleural Mesothelioma, Asbestos Exposure, Angiogenesis.

Related studies

• 3-O-Methylfunicone, a metabolite produced by Penicillium pinophilum, modulates ERK1/2 activity, affecting cell motility of human mesothelioma cells — E. Buommino, I. Paoletti, et al. (2010)
• Modulation of Calretinin Expression in Human Mesothelioma Cells Reveals the Implication of the FAK and Wnt Signaling Pathways in Conferring Chemoresistance towards Cisplatin — J. Wörthmüller, V. Salicio, et al. (2019)
• Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells — B. Han, H.C. Lee-Okada, et al. (2020)
• In vitro and in vivo therapeutic efficacy of the PPAR-γ agonist troglitazone in combination with cisplatin against malignant pleural mesothelioma cell growth — N. Hamaguchi, H. Hamada, et al. (2010)
• ADP sensitizes ZL55 cells to the activity of cisplatin — A. Muscella, L.G. Cossa, et al. (2019)
• Overexpression or absence of calretinin in mouse primary mesothelial cells inversely affects proliferation and cell migration — W. Blum, L. Pecze, et al. (2015)

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