Inhibition of malignant mesothelioma cell matrix metalloproteinase production and invasion by a novel nutrient mixture

Our plain-English summary of Inhibition of malignant mesothelioma cell matrix metalloproteinase production and invasion by a novel nutrient mixture, by M.W. Roomi, V. Ivanov, T. Kalinovsky, et al (Experimental Lung Research, 2006).

The study

• Authors: M.W. Roomi, V. Ivanov, T. Kalinovsky, A. Niedzwiecki, M. Rath
• Journal: Experimental Lung Research
• Published: 2006;32(3-4):69-79
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma (MM), an asbestos-associated cancer with no known cure, is a highly aggressive tumor causing profound morbidity and nearly universal mortality. Extracellular matrix (ECM) matrix metalloproteinases (MMPs) produced by tumor and stromal cells play a key role in tumor invasion and metastasis. Prevention of ECM degradation by MMP inhibition has been shown to be a promising therapeutic approach to inhibition of cancer development. Based on reported anticancer properties, the authors investigated the effect of a mixture (NM) containing lysine, proline, ascorbic acid, and green tea extract on MM cell line MSTO-211 H proliferation (by [MTT] [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay), MMP secretion (by gelatinase zymography), invasion (through Matrigel), and morphology (by hematoxylin and eosin [H&E] staining). MMP-2 and phorbol 12-myristate 13-acetate (PMA)-induced MMP-9 secretion were inhibited by NM in a dose-dependent fashion, with virtual total inhibition at 500 microg/ml NM. Invasion through Matrigel was inhibited at 50, 100, and 500 microg/ml by 27%, 36%, and 100%, respectively. NM was not toxic to the MM cell line, and H&E staining did not indicate any changes at and below 100 microg/ml concentration. In conclusion, NM significantly inhibited MM cell MMP secretion and invasion-both important parameters for cancer prevention, suggesting NM is an effective treatment strategy for MM.

In plain English

This was a laboratory study of human malignant mesothelioma cells grown in culture. It did not involve patients, and it did not test asbestos. The authors treated one mesothelioma cell line, MSTO-211H, with a nutrient mixture containing vitamin C, lysine, proline, arginine, N-acetylcysteine, green tea extract, selenium, copper and manganese, at 0 to 1000 micrograms per milliliter. They measured cell growth, secretion of two tissue-degrading enzymes (MMP-2, and MMP-9 after stimulation with a chemical called PMA), and how many cells invaded through a gel layer called Matrigel. Growth fell by less than 10% at 100, 500 and 1000 micrograms per milliliter, which was not statistically significant (P = .47). Secretion of both enzymes fell as the dose rose, with virtually total inhibition at 500. Invasion was reduced by 27% at 50, 36% at 100, and 100% at 500 micrograms per milliliter. Staining showed no changes in cell appearance at and below 100. The authors concluded that the mixture is a promising candidate for treating mesothelioma. They said other mesothelioma cell lines need to be studied.

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: In vitro laboratory experiment on a cultured human cancer cell line (no patients, no animals in this study)
• Who was studied: One human malignant mesothelioma cell line, MSTO-211H, obtained from the American Type Culture Collection; each dose was tested in triplicate
• Exposure: No asbestos exposure was studied. Cells were treated with a nutrient mixture (vitamin C, L-lysine, L-proline, L-arginine, N-acetylcysteine, green tea extract, selenium, copper, manganese) at 0, 10, 50, 100, 500 and 1000 micrograms per milliliter. Some cells were also treated with PMA at 200 ng/mL to induce MMP-9 secretion.
• Main results:
  • In the mesothelioma cells, the mixture caused a slight decrease (less than 10%) in cell proliferation at 100, 500 and 1000 micrograms per milliliter, which was not statistically significant (P = .47)
  • The mixture inhibited secretion of MMP-2, and of PMA-induced MMP-9, by the mesothelioma cells in a dose-dependent fashion, with virtual total inhibition at 500 micrograms per milliliter
  • Invasion of mesothelioma cells through Matrigel was inhibited by 27% at 50 micrograms per milliliter (P = .002), 36% at 100 (P = .009), and 100% at 500 (P less than .001)
  • Hematoxylin and eosin staining showed no morphological changes in the cells at and below 100 micrograms per milliliter
• The authors' conclusion: The authors concluded that the tested formulation is a promising candidate for therapeutic use in treating mesothelioma, by inhibiting MMP secretion and invasion, while noting that other cell lines need testing
• Limitations the authors state:
  • Only one mesothelioma cell line was tested. The authors stated that further studies on other mesothelioma cell lines are needed to see whether they respond the same way.

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, Metastasis.

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• Matrix Metalloproteinases Polymorphisms as Prognostic Biomarkers in Malignant Pleural Mesothelioma — D. Štrbac, K. Goričar, et al. (2017)
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