Anti-tumor activity of BML Proteases in Breast Cancer, Prostate Cancer and Cervical Cancer by Up-regulation of p53 gene, NF-kB and COX-2 expression through targeting MAPK Pathway

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  • Abstract

    Chemo impediment impels the quest for moreover single targeted or brew of multi-targeted agents. BML proteases, potential agent in this regard, is a pharmacologically active compound, present in stems and fruits of Ananas comosus, endowed with anti-inflammatory, anti-invasive and antimetastatic properties. BML protease is a complex or proteolytic enzymes. These proteolytic enzymes are paraphernalia that promise an impressive number of medical and therapeutic uses, particularly as anti-tumor agents (Swaroop G et al. 2013, p.80). BML proteases is a pharmacologically active compound, present in stems and immature fruits of pineapples (Ananas comosus), which has been shown to have anti-edematous, anti-inflammatory, anti-thrombotic and anti-metastatic properties (Swaroop G et al. 2013, p.80). In the present study anti-tumorigenic activity of BML was recorded in HeLa, MCF 7 and PC3 cell lines. Results showed that BML proteases application delayed the onset of tumorigenesis and reduced the cumulative number of tumors, tumor volume and the average number of tumor cells. To establish a cause and effect relationship, we targeted the proteins involved in the cell death pathway. BML proteases treatment resulted in up-regulation of p53 gene and subsequent activation of caspase 3 and caspase 9 with concomitant decrease in anti-apoptotic protein Bcl-2 in cancer cells targeting intrinsic pathway of apoptosis. BML treatment attenuated phosphorylation of extracellular signal regulated protein kinase (ERK1/2) and mitogen-activated protein kinase (MAPK). Taken together, we conclude that BML induces apoptosis-related proteins by blocking the MAPK kinase signaling in tumor cells, which may account for its anti-tumorigenic effects. Flow cytometry studies were carried out for the study of cell cycle progression.

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      1. Swaroop G, Geetha Viswanathan, Isolation and Characterization of Bromelain (BML) Proteases from Ananas comosus an asset to Cancer Chemotherapy, International Journal of Pharmacology and Toxicology, 1 (2) (2013) 82-90 Science Publishing Corporation
      2. Neetu Kalra, Kulpreet Bhui, Preeti Roy, Smita Srivastava, Jasmine George, Sahdeo Prasad, Yogeshwer Shukla, Regulation of p53, nuclear factor ?B and cyclooxygenase-2 expression by bromelain through targeting mitogen-activated protein kinase pathway in mouse skin, Toxicology and Applied Pharmacology 226 (2008) 3037.
      3. Lauren Pecorino, Molecular Biology of Cancer, 2nd Edition, Oxford University Press, New York, 2008
      4. Slater, al Biochem.Biophysics Acta 77:383 (1963)
      5. Van de Loosdrecht. A.A., Journal of Immunology Methods 174: 311-320 (1994).
      6. Alley, al, Cancer Research 48: 589-601, (1988)
      7. Darzynkiewicz', S. Bruno, G. Del Bino, W. Gorczyca, M.A. Hotz, P. Lassota, and F. Traganos, Features of Apoptotic Cells Measured by Flow Cytometry, Cytometry 13:795-808 (1992)
      8. Carlo Riccardi & Ildo Nicoletti, Analysis of apoptosis by propidium iodide staining and flow cytometry, Nature Protocols 1, -1458 - 1461 (2006)




Article ID: 1455
DOI: 10.14419/ijpt.v2i1.1455

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