Differences in the Inhibitory Specificity Distinguish the Efficacy of Plant Protease Inhibitors on Mouse Fibrosarcoma

Autor(es)

Yoo Im, Sonia ^[1] ; Ramalho Bonturi, Camila ^[1] ; Miti Nakahata, Adriana ^[2] ; Ryuichi Nakaie, Clovis ^[3] ; Pott, Arnildo ^[4] ; Pott, Vali Joana ^[4] ; Vilela Oliva, Maria Luiza ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo UNIFESP, Dept Bioquim, BR-04044020 Sao Paulo, SP - Brazil

^[2] AC Camargo Canc Ctr, Ctr Int Pesquisa CIPE, Lab Genom & Biol Mol, BR-01508010 Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo UNIFESP, Dept Biofis, BR-04044020 Sao Paulo, SP - Brazil

^[4] Univ Fed Mato Grosso do Sul UFMS, Dept Biol, BR-79070900 Campo Grande, MS - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLANTS-BASEL; v. 10, n. 3 MAR 2021.
• Citações Web of Science: 0

Resumo

Metastasis, the primary cause of death from malignant tumors, is facilitated by multiple protease-mediated processes. Thus, effort has been invested in the development of protease inhibitors to prevent metastasis. Here, we investigated the effects of protease inhibitors including the recombinant inhibitors rBbKI (serine protease inhibitor) and rBbCI (serine and cysteine inhibitor) derived from native inhibitors identified in Bauhinia bauhinioides seeds, and EcTI (serine and metalloprotease inhibitor) isolated from the seeds of Enterolobium contortisiliquum on the mouse fibrosarcoma model (lineage L929). rBbKI inhibited 80% of cell viability of L929 cells after 48 h, while EcTI showed similar efficacy after 72 h. Both inhibitors acted in a dose and time-dependent manner. Conversely, rBbCI did not significantly affect the viability of L929 cells. Confocal microscopy revealed the binding of rBbKI and EcTI to the L929 cell surface. rBbKI inhibited approximately 63% of L929 adhesion to fibronectin, in contrast with EcTI and rBbCI, which did not significantly interfere with adhesion. None of the inhibitors interfered with the L929 cell cycle phases. The synthetic peptide RPGLPVRFESPL-NH2, based on the BbKI reactive site, inhibited 45% of the cellular viability of L929, becoming a promising protease inhibitor due to its ease of synthesis. (AU)

• Processo FAPESP: 17/07972-9 - Desenvolvimento de compostos para profilaxia e tratamento de doenças cardiovasculares
• Beneficiário: Maria Luiza Vilela Oliva
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/06630-7 - Fragmentos derivados de proteínas com seletividade para inibição de enzimas de mamíferos e micro-organismos e seu papel como agente anti-inflamatório, antimicrobiano, antitrombótico e antitumoral: mecanismo de ação
• Beneficiário: Maria Luiza Vilela Oliva
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/22243-9 - Fragmentos derivados de proteínas com seletividade para inibição de enzimas de mamíferos e micro-organismos e seu papel como agente anti-inflamatório, antimicrobiano, antitrombótico e antitumoral: mecanismo de ação
• Beneficiário: Camila Ramalho Bonturi
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado