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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Imaging Sites of Inhibition of Proteolysis in Pathomimetic Human Breast Cancer Cultures by Light-Activated Ruthenium Compound

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Author(s):
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Ramalho, Suelem D. [1] ; Sharma, Rajgopal [2] ; White, Jessica K. [3] ; Aggarwal, Neha [4] ; Chalasani, Anita [5] ; Sameni, Mansoureh [5] ; Moin, Kamiar [5, 6] ; Vieira, Paulo C. [1] ; Turro, Claudia [3] ; Kodanko, Jeremy J. [2] ; Sloane, Bonnie F. [5, 6]
Total Authors: 11
Affiliation:
[1] Univ Fed Sao Carlos, Dept Chem, Sao Paulo - Brazil
[2] Wayne State Univ, Dept Chem, Detroit, MI 48202 - USA
[3] Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 - USA
[4] Wayne State Univ, Sch Med, Dept Physiol, Detroit, MI 48201 - USA
[5] Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 - USA
[6] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI - USA
Total Affiliations: 6
Document type: Journal article
Source: PLoS One; v. 10, n. 11 NOV 12 2015.
Web of Science Citations: 12
Abstract

The cysteine protease cathepsin B has been causally linked to progression and metastasis of breast cancers. We demonstrate inhibition by a dipeptidyl nitrile inhibitor (compound 1) of cathepsin B activity and also of pericellular degradation of dye-quenched collagen IV by living breast cancer cells. To image, localize and quantify collagen IV degradation in real-time we used 3D pathomimetic breast cancer models designed to mimic the in vivo microenvironment of breast cancers. We further report the synthesis and characterization of a caged version of compound 1, {[}Ru(bpy)(2)(1)(2)](BF4)(2) (compound 2), which can be photoactivated with visible light. Upon light activation, compound 2, like compound 1, inhibited cathepsin B activity and pericellular collagen IV degradation by the 3D pathomimetic models of living breast cancer cells, without causing toxicity. We suggest that caged inhibitor 2 is a prototype for cathepsin B inhibitors that can control both the site and timing of inhibition in cancer. (AU)