Elucidating the Molecular Mechanisms of Anacardic Acid and Biacacetin Mediated Regulation of Matrix Metalloproteinases in Cancer
Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries like India. An in-depth understanding of the molecular mechanisms involved in the progression of different forms of cancer has been the focus of drug discovery efforts. Development of Matrix Metalloproteinase inhibitors as anti-cancer therapeutics has been a major consideration in the drug development arena for the past few decades, the reason being elevated levels of Matrix Metalloproteinases (MMPs) observed in several cancers. Among the several isoforms of MMPs, Gelatinases (MMP-2 and MMP-9) and MT1-MMP, a membrane bound activator of MMP-2/9, play a prominent role in metastasis by cleaving the major components of the extracellular matrix. Natural products have been an invaluable repository for the discovery of novel drug candidates as a source of remedy for a number of ailments including cardiovascular diseases and cancers. One such valuable source of natural product is anacardic acid isolated from Cajueiro or cashew (Anacardium occidentale). Similarly flavonoids form another group of natural products that are found in several fruits and vegetables and are well known to exhibit a variety of pharmacological properties. The present study aims at understanding the regulation of MMPs by Anacardic acid and Biacacetin (a biflavonoid). Additionally, the study focuses on determining how these compounds mediate the molecular crosstalk between the EGF cascade and MMPs. These studies therefore will potentially help to utilize Anacardic acid and Biacacetin as novel templates to design effective drugs for cancer therapy.
Gelatin degradation assay showing the reduction in degradation of the fluorescent gelatin at 5 μM concentration of Biacacetin 9h when compared to control.
Collaborators: Dr. L. Ravi Shankar, NIST, Trivandrum