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RECK and TIMP-2 mediate inhibition of MMP-2 and MMP-9 by Annona muricata

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Abstract

Up-regulation of MMP-2 and MMP-9 plays a significant role in promoting cancer progression by degrading the components of the extracellular matrix, thereby enhancing the migration of tumor cells. Although the anti-proliferative and apoptotic effect of Annona muricata is well established, its effect on MMP-2 and MMP-9, a major target in several types of cancers, has not been studied. Powdered samples of various parts of A. muricata like fruit, stem, seed, and twig extracted using aqueous methanol showed significant dose-dependent inhibition of MMP-2 and MMP-9 in a highly metastatic fibrosarcoma cell line, HT1080. Additionally, these extracts also up-regulated the expression of several endogenous inhibitors of MMP-2 and MMP-9 like REversion-inducing Cysteine-rich protein with Kazal motifs (RECK) and Tissue Inhibitor of Metalloproteinase-2 (TIMP-2). Furthermore, primary cells developed from tumor tissues obtained from patients not exposed to chemotherapy, also exhibited similar results. Remarkably, the inhibition of MMP-2 and MMP-9 observed was tumor specific, with the A. muricata fruit extract showing only 2% inhibition in cells obtained from normal tissues, when compared to 60% inhibition observed in cells obtained from tumor samples. The present study elucidates a novel mechanism by which A. muricata extracts selectively exhibit their anti-cancer activity in tumor cells by down-regulating MMP-2 and MMP-9 that are important biomarkers in cancer.

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Acknowledgements

We acknowledge Mata Amritanandamayi Devi, Chancellor, Amrita Vishwa Vidyapeetham (Amrita University), for being the inspiration behind this study. We would like to acknowledge Dr CM Sreejith, SNM College, Kerala, India, for helping with the process of herbarium preparation and obtaining the accession number. We acknowledge Amrita Agilent Research Centre for providing mass spectrometry data and Dr Prakash Chandran, Department of Chemistry, M.M.N.S.S. College, Kottayam, Kerala, for helping with the analysis of mass spectrometry data. This work was supported by Institutional funding (Amrita University Research) grant (BGN).

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Authors and Affiliations

  1. Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Clappana P.O, Kollam, 690 525, India

    G Drishya, Jyotsna Nambiar, Sanu K Shaji, Muralidharan Vanuopadath, A Achuthan, Abishek Kumar, Ashna Alias, Ayesha Sherif, Catherine Joseph, P Divya, Damu Sunil Kumar, Chinchu Bose, Sobha Vijayan Nair, S Sudarslal, Geetha B Kumar & Bipin G Nair

  2. Laboratory of Molecular Medicine, Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram, 695 011, India

    S Lakshmi

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  1. G Drishya
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  2. Jyotsna Nambiar
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Corresponding author

Correspondence to Bipin G Nair.

Additional information

Communicated by Rita Mulherkar.

Corresponding editor: Rita Mulherkar

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Drishya, G., Nambiar, J., Shaji, S.K. et al. RECK and TIMP-2 mediate inhibition of MMP-2 and MMP-9 by Annona muricata. J Biosci 45, 89 (2020). https://doi.org/10.1007/s12038-020-00056-z

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  • DOI: https://doi.org/10.1007/s12038-020-00056-z

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