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

Autor(es):Mostrar menos -

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 10, n. 11 NOV 12 2015.
• Citações Web of Science: 12

Resumo

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)

• Processo FAPESP: 10/52326-9 - Estudo de produtos naturais oriundos de plantas do cerrado e mata atlântica: conhecimento químico-biológico aliado à preservação
• Beneficiário: Paulo Cézar Vieira
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Regular