Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in human lung cancer and mesothelioma cell lines

Our plain-English summary of Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in human lung cancer and mesothelioma cell lines, by M.W. Roomi, T. Kalinovsky, A. Niedzwiecki, et al (International Journal of Oncology, 2013).

The study

• Authors: M.W. Roomi, T. Kalinovsky, A. Niedzwiecki, M. Rath
• Journal: International Journal of Oncology
• Published: 2013;42(6):1883-9
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Lung cancer, the most prevalent cancer worldwide and malignant mesothelioma are highly aggressive tumors that are characterized by high levels of matrix metalloproteinase (MMP)-2 and -9 secretion. Proteases play a key role in tumor cell invasion and metastasis by digesting the basement membrane and ECM components. Strong clinical and experimental evidence demonstrates association of elevated levels of u-PA and MMPs with cancer progression, metastasis and shortened patient survival. MMP activities are regulated by specific tissue inhibitors of metalloproteinases (TIMPS). Our main objective was to study the effect of a nutrient mixture (NM) on the activity of u-PA, MMPs and TIMPs on human lung and malignant mesothelioma (MM) cell lines. Human lung cancer (A-549 and Calu-3) and malignant mesothelioma (MSTO-211H) cell lines were cultured in their respective media and treated at confluence with NM at 0, 50, 100, 250, 500 and 1000 µg/ml. Analysis of u-PA activity was carried out by fibrin zymography, MMPs by gelatinase zymography and TIMPs by reverse zymography. Both lung cancer cell lines expressed u-PA, which was inhibited by NM in a dose-dependent manner. However, no bands corresponding to u-PA were detected for the MSTO-211H MM cell line. On gelatinase zymography, A-549 cells showed one band corresponding to MMP-2 and induction of MMP-9 with PMA (100 ng/ml) treatment. MSTO-211H showed two bands, an intense band corresponding to MMP-2 and a faint band corresponding to MMP-9; MMP-9 was enhanced significantly with PMA treatment. NM inhibited their expression in both cell lines in a dose-dependent manner. Calu-3 showed no MMP-2 or MMP-9 expression. Activity of TIMPs was upregulated by NM in all cancer cell lines in a dose-dependent manner. Analysis revealed a positive correlation between u-PA and MMPs and a negative correlation between u-PA/MMPs and TIMPs. These findings suggest the therapeutic potential of NM in the treatment of lung and mesothelioma cancers.

In plain English

This laboratory experiment used human cancer cells, not people, and did not study asbestos exposure. The authors treated two lung cancer cell lines (A-549 and Calu-3) and one malignant mesothelioma cell line (MSTO-211H) with a nutrient mixture. It contained vitamin C, lysine, proline, arginine, N-acetyl cysteine, green tea extract, selenium, copper and manganese, and was tested at doses up to 1000 µg/ml. They measured enzymes linked to tissue breakdown (u-PA, MMP-2 and MMP-9) and an enzyme inhibitor (TIMP-2). Both lung cancer lines produced u-PA, and it fell as the dose rose. The mesothelioma line showed no u-PA. Untreated A-549 cells made MMP-2, but MMP-9 appeared only after PMA treatment. The mesothelioma cells showed an intense MMP-2 band and a faint MMP-9 band, which PMA enhanced. In both lines, the mixture fully blocked MMP-2 and MMP-9 at 500 µg/ml. Calu-3 cells showed no MMP-2 or MMP-9. TIMP-2 activity rose with dose in all three cell lines. TIMP-2 moved opposite to u-PA or the MMPs. The authors concluded that the mixture showed "potent anticancer activity" against mechanisms behind the spread of lung cancer and malignant mesothelioma.

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) experiment on cultured human cancer cell lines
• Who was studied: Three human cancer cell lines: lung cancer lines A-549 and Calu-3, and malignant mesothelioma line MSTO-211H. No patients were studied.
• Exposure: A nutrient mixture (NM) of vitamin C, L-lysine, L-proline, L-arginine, N-acetyl cysteine, green tea extract, selenium, copper and manganese, given to cells at 0, 50, 100, 250, 500 and 1000 µg/ml. Some cultures were also treated with PMA (100 ng/ml) to induce MMP-9. No asbestos exposure was studied.
• Main results:
  • u-PA activity fell with increasing NM dose in both lung cancer lines. Activity was virtually blocked at 250 µg/ml in A-549 cells (linear trend R2=0.563) and at 1000 µg/ml in Calu-3 cells (linear trend R2=0.680).
  • No u-PA was detected in the mesothelioma cell line MSTO-211H.
  • Untreated A-549 lung cancer cells showed MMP-2. MMP-9 was induced only with PMA (100 ng/ml) treatment.
  • In A-549 cells, NM reduced MMP-2 and MMP-9 as the dose rose, with total block at 500 µg/ml (linear trend R2=0.781 for MMP-2 and 0.722 for MMP-9).
  • MSTO-211H mesothelioma cells showed an intense MMP-2 band and a faint MMP-9 band. MMP-9 was significantly enhanced with PMA treatment.
  • In MSTO-211H mesothelioma cells, NM completely blocked MMP-2 and MMP-9 at 500 µg/ml (linear trend R2 = 0.849 for MMP-2 and R2=0.853 for MMP-9).
  • Calu-3 lung cancer cells showed no MMP-2 or MMP-9.
  • TIMP-2 activity increased with NM dose in all three cancer cell lines.
  • In A-549 cells, u-PA and MMP-2 were positively correlated (r=0.679). TIMP-2 was negatively correlated with u-PA (r=-0.685) and with MMP-2 (r=-0.862).
  • TIMP-2 was negatively correlated with u-PA in Calu-3 cells (r=-0.674) and with MMP-9 in MSTO-211H mesothelioma cells (r=-0.925).
• The authors' conclusion: The authors concluded that the nutrient mixture showed "potent anticancer activity" by acting on mechanisms responsible for the spread of lung cancer and malignant mesothelioma. They wrote that the in vitro results suggest its potential in modulating lung cancer invasion and metastasis.

Topics

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

Medical terms in this study, explained in our Lexicon: Lung Cancer, Mesothelioma, Malignant Mesothelioma, Metastasis.

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