3-O-Methylfunicone, a metabolite produced by Penicillium pinophilum, modulates ERK1/2 activity, affecting cell motility of human mesothelioma cells

Our plain-English summary of 3-O-Methylfunicone, a metabolite produced by Penicillium pinophilum, modulates ERK1/2 activity, affecting cell motility of human mesothelioma cells, by E. Buommino, I. Paoletti, A. De Filippis, et al (Cell Proliferation, 2010).

The study

• Authors: E. Buommino, I. Paoletti, A. De Filippis, R. Nicoletti, M.L. Ciavatta, S. Menegozzo, M. Menegozzo, M.A. Tufano
• Journal: Cell Proliferation
• Published: 2010;43(2):114-23
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: 3-O-methylfunicone (OMF), a secondary metabolite produced by Penicillium pinophilum, affects cell proliferation and motility in a variety of human solid tumours. The aim of this study was to demonstrate whether OMF has the ability to arrest cell division and motility, in a human mesothelioma cell line. Malignant mesothelioma is an aggressive cancer that does not respond to standard therapies the cells of which are considered to be highly resistant to apoptosis.

Material And Methods: Cell motility and invasion were measured using a modified Boyden chamber. Gene expression was examined by RT-PCR, while ERK1/2 was investigated by Western blot analysis. All experiments were also performed on primary cultures of mesothelial cells.

Results: The present study shows that OMF inhibited motility of the NCI mesothelioma cell line by modulating ERK signalling activity, and affected alphaVbeta5 integrin and MMP-2 expression, inducing marked downregulation at both mRNA and protein levels. Substantial downregulation of VEGF gene expression was also demonstrated. These effects were not observed in normal mesothelial cell cultures.

Conclusion: OMF may have potential as a naturally derived anti-tumour drug for treatment of mesothelioma.

In plain English

This was a laboratory study of cells grown in dishes, not of people. The authors tested 3-O-methylfunicone (OMF), a substance made by the soil fungus Penicillium pinophilum, on three kinds of cells: a human mesothelioma cell line (NCI-H2452), cells grown from a malignant pleural mesothelioma biopsy, and non-malignant mesothelial cells grown from a second patient's pleural biopsy. The study did not examine asbestos exposure. Most tests used 50 micrograms per millilitre of OMF for 48 hours. In the mesothelioma cell line, OMF slowed cell growth, reduced cell migration by 67% and reduced invasion through a gel barrier by 41%. In the cells from the mesothelioma biopsy, growth fell by 52%, migration by 42% and invasion by 34%. In the cell line, OMF lowered the activity of the ERK1/2 signalling proteins. It also reduced alpha-V and beta-5 integrin, MMP-2 and VEGF, molecules linked to cell movement, tissue breakdown and blood vessel growth. These effects were not seen in the normal mesothelial cells. The authors concluded that OMF might be a promising treatment compound for mesothelioma, and that studies in living (in-vivo) models may further clarify its effects.

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: NCI-H2452 human mesothelioma cell line (NCI); primary cultures of non-malignant mesothelial cells (Mes1) and mesothelioma cells (Mest) grown from pleural biopsies of two patients
• Exposure: 3-O-methylfunicone (OMF), extracted from the fungus Penicillium pinophilum; tested at 25, 50 and 100 micrograms per millilitre for 24, 48 and 72 hours, with 50 micrograms per millilitre for 48 hours used for most experiments; a MEK inhibitor (U0126) was used for comparison. Asbestos exposure was not studied.
• Main results:
  • In NCI mesothelioma cells, 50 micrograms per millilitre OMF for 48 hours gave the best growth inhibition with minor cell-shape changes
  • In normal mesothelial cells (Mes1), OMF did not affect proliferation or cell shape, which the authors took to mean the toxic effect was more specific to mesothelioma cells
  • NCI cell migration was inhibited by 67% compared with untreated cells
  • OMF did not change the motility of Mes1 normal mesothelial cells
  • NCI cell invasion through a matrigel-coated filter was reduced by 41% after 48 hours of OMF; Mes1 cells could not invade the filters at all
  • In primary mesothelioma cells (Mest), OMF inhibited growth by 52%
  • In Mest cells, migration was reduced by 42% and invasion by 34%
  • OMF markedly decreased alpha-V and beta-5 integrin gene expression in NCI cells but not in Mes1 cells
  • MMP-2 expression decreased in NCI cells after 48 hours of OMF
  • OMF decreased all three VEGF isoforms in NCI cells
  • OMF reduced ERK1/2 activity in NCI cells at 24 and 48 hours, comparable to the MEK inhibitor U0126, but did not change ERK activity in Mes1 cells
• The authors' conclusion: The authors concluded that OMF might be a promising chemotherapeutic compound for human mesothelioma, and that studies in in-vivo models may further clarify its therapeutic effects

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Malignant Mesothelioma, Apoptosis, Mesothelial Cells.

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