Evaluation of Extracellular Endosulfatase HSULF-2 in Breast Cancer Cell WNT Signaling and Its Inhibition by a Sulfate Ester Derivative of Synthetic Antioxidant
Abstract
The research results we obtained in this Army Concept grant include the following novel findings. A) We showed that 2,4- disulfonyl-phenyl-tert-butylnitrone (2,4-SPBN) acts as a weak inhibitor of the enzymatic activity of the extracellular endosulfatase Sulf2 when the enzyme is acting as an aryl sulfatase on the substrate 4-methyllumbelliferyl-O-sulfate (4-MUS) and that 2,4-SPBN was much more effective enzyme inhibitor when Sulf2 acts upon its natural substrate the 6-O-sulfate ester of heparin sulfate. B) We also made the novel observation that Sulf2 activity was inactivated by hydrogen peroxide. C) We also showed that the phenyl sulfonyl anti-cancer agent suramin very potently inhibited Sulf2 enzymatic activity. D) Utilizing a Balb/c nude mouse model we showed that tumor growth of MCF-7 human breast cancer cells was significantly suppressed by administering 2,4-SPBN in the drinking water at 250 mg/kg at 35 days when experiments had to be stopped. These novel observations help us understand the anti-cancer activity of 2,4-SPBN and the potential role of Sulf2 inhibitors as anti-cancer agents and the potential for novel phenyl-sulfonyl agents as possible breast cancer therapeutics.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2010
- Accession Number
- ADA570593
Entities
People
- Robert A. Floyd
Organizations
- Oklahoma Medical Research Foundation