The effects of a plant proteinase inhibitor from Enterolobium contortisiliquum on human tumor cell lines

Abstract

Supplementary to the efficient inhibition of trypsin, chymotrypsin, plasma kallikrein, and plasmin already described by the EcTI inhibitor from Enterolobium contortisiliquum, it also blocks human neutrophil elastase (K iapp s4.3 nM) and prevents phorbol ester (PMA)-stimulated activation of matrix metalloproteinase (MMP)-2 probably via interference with membrane-type 1 (MT1)-MMP. Moreover, plasminogeninduced activation of proMMP-9 and processing of active MMP-2 was also inhibited. Furthermore, the effect of EcTI on the human cancer cell lines HCT116 and HT29 (colorectal), SkBr-3 and MCF-7 (breast), K562 and THP-1 (leukemia), as well as on human primary fibroblasts and human mesenchymal stem cells (hMSCs) was studied. EcTI inhibited in a concentration range of 1.0-2.5 mM rather specifically tumor cell viability without targeting primary fibroblasts and hMSCs. Taken together, our data indicate that the polyspecific proteinase inhibitor EcTI prevents proMMP activation and is cytotoxic against tumor cells without affecting normal tissue remodeling fibroblasts or regenerative hMSCs being an important tool in the studies of tumor cell development and dissemination.

Enterolobium contortisiliquum Trypsin Inhibitor (EcTI), a Plant Proteinase Inhibitor, Decreases in Vitro Cell Adhesion and Invasion by Inhibition of Src Protein-Focal Adhesion Kinase (FAK) Signaling Pathways

“…To date the major contribution in cancer invasion attributed to MMPs is the degradation of the ECM barrier (1,22,23). To carry out such function, MMPs are expected to act at the leading edge of the invading cancer cells.…”

“…Many studies suggest the use of proteinase inhibitors in cancer therapy (23,(27)(28)(29)(30). Increased proteolysis has been shown to underpin various pathological processes, and as a result, proteinases and proteinase inhibitors have emerged as potential therapeutic targets.…”

“…Increased proteolysis has been shown to underpin various pathological processes, and as a result, proteinases and proteinase inhibitors have emerged as potential therapeutic targets. There are many examples of therapeutic interventions using proteinase inhibitors: angiotensin-converting enzyme inhibitors for the treatment of hypertension (31), HIV aspartyl proteinase inhibitors to prevent the development of AIDS (30,32), and application of proteinase inhibitors in the treatment of cancer (23,33,34).…”

Extraction, purification and characterization of inhibitor of trypsin from Chenopodium quinoa seeds

“…They are widely distributed in the plant kingdom and the plant families Leguminoseae, Solanaceae and Graminaceae are known to be rich in these inhibitors (Nakahata et al, 2011). The PIs are small regulatory proteins generally present in high concentration and distributed in 10 families or more determined according to the primary structure, that is, the active amino acid in their reactive site, which are serine-, cysteine-, aspartic-, and metallo-PIs (Losso, 2008).…”

Efeito do inibidor de proteinase de origem vegetal EcTI, sobre a lesão pulmonar induzida pela elastase em camundongos C57BI6

“…Uma investigação sobre as propriedades biológicas do EcTI concluiu que este inibidor de proteinase não demonstrou nenhum efeito sobre a proliferação de células cancerígenas no estômago ou fibroblastos, mas foi capaz de inibir a adesão, migração e invasão destas células cancerígenas no estômago, sem efeito sobre a adesão de fibroblastos (Nakahata et al, 2011;De Paula et al, 2012).…”