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

  • Authors:
    • M. Waheed Roomi
    • Tatiana Kalinovsky
    • Matthias Rath
    • Aleksandra Niedzwiecki
  • View Affiliations / Copyright

    Affiliations: Dr. Rath Research Institute, Santa Clara, CA, USA
    Copyright: © Roomi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 768-776
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    Published online on: June 20, 2012
       https://doi.org/10.3892/or.2012.1879
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Abstract

Cancers of the breast, cervix, uterus and ovary are the most prevalent cancers in women worldwide. 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 urokinase plasminogen activators (u-PA) and matrix metalloproteinases (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 in human breast, cervix, uterine and ovarian cancer cell lines. Human breast (MDA-MB-231 and MCF-7), cervical (HeLa), uterine (SK-UT-1) and ovarian (SKOV3) cancer 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 breast and uterine 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 HeLa and SK-OV-3 cell lines. On gelatinase zymography, MDA-MB-231 and MCF-7 showed one band corresponding to MMP-9, HeLa showed two bands, an intense band corresponding to MMP-2 and a faint band corresponding to MMP-9, SK-UT-1 showed PMA-induced MMP-9, and SK-OV-3 showed a band corresponding to MMP-2. NM inhibited their expression in all cell lines. The activity of TIMPs was upregulated 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 female cancers.
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Copy and paste a formatted citation
Spandidos Publications style
Roomi MW, Kalinovsky T, Rath M and Niedzwiecki A: Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in human female cancer cell lines. Oncol Rep 28: 768-776, 2012.
APA
Roomi, M.W., Kalinovsky, T., Rath, M., & Niedzwiecki, A. (2012). Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in human female cancer cell lines. Oncology Reports, 28, 768-776. https://doi.org/10.3892/or.2012.1879
MLA
Roomi, M. W., Kalinovsky, T., Rath, M., Niedzwiecki, A."Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in human female cancer cell lines". Oncology Reports 28.3 (2012): 768-776.
Chicago
Roomi, M. W., Kalinovsky, T., Rath, M., Niedzwiecki, A."Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in human female cancer cell lines". Oncology Reports 28, no. 3 (2012): 768-776. https://doi.org/10.3892/or.2012.1879
Copy and paste a formatted citation
x
Spandidos Publications style
Roomi MW, Kalinovsky T, Rath M and Niedzwiecki A: Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in human female cancer cell lines. Oncol Rep 28: 768-776, 2012.
APA
Roomi, M.W., Kalinovsky, T., Rath, M., & Niedzwiecki, A. (2012). Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in human female cancer cell lines. Oncology Reports, 28, 768-776. https://doi.org/10.3892/or.2012.1879
MLA
Roomi, M. W., Kalinovsky, T., Rath, M., Niedzwiecki, A."Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in human female cancer cell lines". Oncology Reports 28.3 (2012): 768-776.
Chicago
Roomi, M. W., Kalinovsky, T., Rath, M., Niedzwiecki, A."Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in human female cancer cell lines". Oncology Reports 28, no. 3 (2012): 768-776. https://doi.org/10.3892/or.2012.1879
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