Popular Artificial Sweetener Could Lead to New Treatments for Aggressive Cancers
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http://www.newswise.com/articles/popular-artificial-sweetener-could-lead-to-new-treatments-for-aggressive-cancers
CONTACT:
Robert McKenna, Ph.D.
University of Florida
Department of Biochemistry and Molecular Biology
College of Medicine
Gainesville, FL 32610
Phone: 352-392-5696
Email: rmckenna@ufl.edu
Title
Saccharin and its carbohydrate-conjugate shows promise for isoform selective inhibition of Carbonic Anhydrase IX: a lead approach to anti-cancer drug development
Abstract
Carbonic anhydrase IX (CA IX) is a zinc metalloenzyme that is highly expressed in several aggressive cancer types and its expression has been linked to a poorer prognosis in patients. Inhibition of CA IX has shown to be advantageous in terms of reducing tumor cell proliferation, growth, and inducing chemo- and radiosensitivity in solid tumors. As such, CA IX has been characterized as an ideal anti-cancer target due to its minimal expression in normal human tissue and its physiochemical properties. Despite inhibition of CA IX showing great therapeutic promise, designing selective CA IX inhibitors has been challenging due to its high homology with other ubiquitously expressed human isoforms. Here we demonstrate that saccharin, the main additive in "Sweet N' Low", can be used as a lead compound for structure-based drug design of CA IX selective inhibitors. Furthermore we show how the linkage of a carbohydrate fragment to saccharin enhances CA IX inhibition by >1000-fold over other isoforms and provide insights into the structure-activity relationships of such compounds. This data presents a new class of CA IX inhibitors that will potentially aide in the treatment of several cancers.