title: Anacardic acid inhibits gelatinases through the regulation of Spry2, MMP-14, EMMPRIN and RECK.
abstract: Earlier studies from our laboratory have identified Anacardic acid (AA) as a potent inhibitor of gelatinases (MMP-2 and 9), which are over-expressed in a wide variety of cancers (Omanakuttan et al., 2012). Disruption of the finely tuned matrix metalloproteinase (MMP) activator/inhibitor balance plays a decisive role in determining the fate of the cell. The present study demonstrates for the first time, that in addition to regulating the expression as well as activity of gelatinases, AA also inhibits the expression of its endogenous activators like MMP-14 and Extracellular Matrix MetalloProteinase Inducer (EMMPRIN) and induces the expression of its endogenous inhibitor, REversion-inducing Cysteine-rich protein with Kazal motifs (RECK). In addition to modulating gelatinases, AA also inhibits the expression of various components of the Epidermal Growth Factor (EGF) pathway like EGF, Protein Kinase B (Akt) and Mitogen-activated protein kinases (MAPK). Furthermore, AA also activates the expression of Sprouty 2 (Spry2), a negative regulator of EGF pathway, and silencing Spry2 results in up-regulation of expression of gelatinases as well as MMP-14. The present study thus elucidates a novel mechanism of action of AA and provides a strong basis for utilizing this molecule as a template for cancer therapeutics.
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Clappana P.O., Kollam 690525, Kerala, India.
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Nambiar
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Clappana P.O., Kollam 690525, Kerala, India.
authors.forename: Chinchu
authors.initials: C
authors.lastname: Bose
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Clappana P.O., Kollam 690525, Kerala, India.
authors.forename: Meera
authors.initials: M
authors.lastname: Venugopal
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Clappana P.O., Kollam 690525, Kerala, India.
authors.forename: Asoke
authors.initials: A
authors.lastname: Banerji
authors.affiliation: Albany College of Pharmacy and Health Sciences, New York, USA.
authors.forename: Tarun B
authors.initials: TB
authors.lastname: Patel
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Clappana P.O., Kollam 690525, Kerala, India.
authors.forename: Geetha B
authors.initials: GB
authors.lastname: Kumar
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Clappana P.O., Kollam 690525, Kerala, India. Electronic address: bipinnair03@gmail.com.
authors.forename: Bipin G
authors.initials: BG
authors.lastname: Nair
mesh_terms: D048729:Anacardic Acids / Q000494:pharmacology*; D051926:Basigin / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000378:metabolism*; D018093:Gelatinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D015398:Signal Transduction / Q000187:drug effects; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
chemical_list: D048729:Anacardic Acids; D058851:GPI-Linked Proteins; D047908:Intracellular Signaling Peptides and Proteins; D061965:Matrix Metalloproteinase Inhibitors; D008565:Membrane Proteins; C115460:RECK protein, human; C485561:SPRY2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; D051926:Basigin; C088115:anacardic acid; D004815:Epidermal Growth Factor; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14
keywords: Anacardic acid; EMMPRIN; Gelatinases; MMP-14; RECK; Spry2