Blocking the Proliferation of Human Tumor Cell Lines by Peptidase Inhibitors from Bauhinia Seeds

Blocking the Proliferation of Human Tumor Cell Lines by Peptidase Inhibitors from Bauhinia Seeds

Author Nakahata, Adriana Miti Autor UNIFESP Google Scholar
Mayer, Barbara Google Scholar
Neth, Peter Google Scholar
Hansen, Daiane Autor UNIFESP Google Scholar
Sampaio, Misako Uemura Autor UNIFESP Google Scholar
Oliva, Maria Luiza Vilela Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Max Planck Inst Biochem
Univ Munich
Abstract In cancer tumors, growth, invasion, and formation of metastasis at a secondary site play a pivotal role, participating in diverse processes in the development of the pathology, such as degradation of extracellular matrix. Bauhinia seeds contain relatively large quantities of peptidase inhibitors, and two Bauhinia inhibitors were obtained in a recombinant form from the Bauhinia bauhinioides species, B. bauhinoides cruzipain inhibitor, which is a cysteine and serine peptidase inhibitor, and B. bauhinioides kallikrein inhibitor, which is a serine peptidase inhibitor. While recombinant B. bauhinoides cruzipain inhibitor inhibits human neutrophil elastase cathepsin G and the cysteine proteinase cathepsin L, recombinant B. bauhinioides kallikrein inhibitor inhibits plasma kallikrein and plasmin. the effects of recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor on the viability of tumor cell lines with a distinct potential of growth from the same tissue were compared to those of the clinical cytotoxic drug 5-fluorouracil. At 12.5 mu M concentration, recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor were more efficient than 5-fluorouracil in inhibiting MKN-28 and Hs746T (gastric), HCT116 and HT29 (colorectal), SkBr-3 and MCF-7 (breast), and THP-1 and K562 (leukemia) cell lines. Additionally, recombinant B. bauhinoides cruzipain inhibitor inhibited 40% of the migration of Hs746T, the most invasive gastric cell line, while recombinant B. bauhinioides kallikrein inhibitor did not affect cell migration. Recombinant B. bauhinioides kallikrein inhibitor and recombinant B. bauhinoides cruzipain inhibitor, even at high doses, did not affect hMSC proliferation while 5-fluorouracil greatly reduced the proliferation rates of hMSCs. Therefore, both recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor might be considered for further studies to block peptidase activities in order to target specific peptidase-mediated growth and invasion characteristics of individual tumors, mainly in patients resistant to 5-fluorouracil chemotherapy.
Keywords Bauhinia bauhinioides
Leguminosae
cancer
cathepsins
5-FU
kallikrein
Kunitz inhibitors
trypsin inhibitor
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2009/53766-5
Date 2013-03-01
Published in Planta Medica. Stuttgart: Georg Thieme Verlag Kg, v. 79, n. 3-4, p. 227-235, 2013.
ISSN 0032-0943 (Sherpa/Romeo, impact factor)
Publisher Georg Thieme Verlag Kg
Extent 227-235
Origin http://dx.doi.org/10.1055/s-0032-1328156
Access rights Closed access
Type Article
Web of Science ID WOS:000315948000006
URI http://repositorio.unifesp.br/handle/11600/36046

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