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https://www.ias.ac.in/article/fulltext/jbsc/045/0089

Annona muricata; fibrosarcoma; MMP-2 and MMP-9; RECK; TIMP-2

Up-regulation of MMP-2 and MMP-9 plays a significant role in promoting cancer progression by degradingthe components of the extracellular matrix, thereby enhancing the migration of tumor cells. Although the antiproliferativeand apoptotic effect of Annona muricata is well established, its effect on MMP-2 and MMP-9, amajor 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-dependentinhibition of MMP-2 and MMP-9 in a highly metastatic fibrosarcoma cell line, HT1080. Additionally, theseextracts also up-regulated the expression of several endogenous inhibitors of MMP-2 and MMP-9 likeREversion-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 notexposed to chemotherapy, also exhibited similar results. Remarkably, the inhibition of MMP-2 and MMP-9observed was tumor specific, with the A. muricata fruit extract showing only 2% inhibition in cells obtainedfrom normal tissues, when compared to 60% inhibition observed in cells obtained from tumor samples. Thepresent study elucidates a novel mechanism by which A. muricata extracts selectively exhibit their anti-canceractivity in tumor cells by down-regulating MMP-2 and MMP-9 that are important biomarkers in cancer.

G DRISHYA¹ JYOTSNA NAMBIAR¹ SANU K SHAJI¹ MURALIDHARAN VANUOPADATH¹ A ACHUTHAN¹ ABISHEK KUMAR¹ ASHNA ALIAS¹ AYESHA SHERIF¹ CATHERINE JOSEPH¹ P DIVYA¹ DAMU SUNIL KUMAR¹ CHINCHU BOSE¹ SOBHA VIJAYAN NAIR¹ S SUDARSLAL¹ GEETHA B KUMAR¹ S LAKSHMI² BIPIN G NAIR¹

1. Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Clappana P.O, Kollam 690 525, India
2. Laboratory of Molecular Medicine, Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram 695 011, India

Published

2 July 2020