A Kunitz-type inhibitor from tick salivary glands: A promising novel antitumor drug candidate

Autor(es)

Lobba, Aline R. M. ; Alvarez-Flores, Miryam Paola ; Fessel, Melissa Regina ; Buri, Marcus Vinicius ; Oliveira, Douglas S. S. ; Gomes, Renata N. N. ; Cunegundes, Priscila S. S. ; DeOcesano-Pereira, Carlos ; Cinel, Victor D. D. ; Chudzinski-Tavassi, Ana M. M.

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN MOLECULAR BIOSCIENCES; v. 9, p. 16-pg., 2022-08-16.

Resumo

Salivary glands are vital structures responsible for successful tick feeding. The saliva of ticks contains numerous active molecules that participate in several physiological processes. A Kunitz-type factor Xa (FXa) inhibitor, similar to the tissue factor pathway inhibitor (TFPI) precursor, was identified in the salivary gland transcriptome of Amblyomma sculptum ticks. The recombinant mature form of this Kunitz-type inhibitor, named Amblyomin-X, displayed anticoagulant, antiangiogenic, and antitumor properties. Amblyomin-X is a protein that inhibits FXa in the blood coagulation cascade and acts via non hemostatic mechanisms, such as proteasome inhibition. Amblyomin-X selectively induces apoptosis in cancer cells and promotes tumor regression through these mechanisms. Notably, the cytotoxicity of Amblyomin-X seems to be restricted to tumor cells and does not affect non-tumorigenic cells, tissues, and organs, making this recombinant protein an attractive molecule for anticancer therapy. The cytotoxic activity of Amblyomin-X on tumor cells has led to vast exploration into this protein. Here, we summarize the function, action mechanisms, structural features, pharmacokinetics, and biodistribution of this tick Kunitz-type inhibitor recombinant protein as a promising novel antitumor drug candidate. (AU)

• Processo FAPESP: 20/13139-0 - Centro de Excelência na Descoberta de Novos Alvos
• Beneficiário: Ana Marisa Chudzinski-Tavassi
• Modalidade de apoio: Auxílio à Pesquisa - Programa Centros de Pesquisa Aplicada
• Processo FAPESP: 18/20469-7 - Usos de moléculas citoprotetoras (hemolina, lipocalina e peptídeos) como ferramentas para a pesquisa de novos alvos moleculares em condrócitos osteoartríticos
• Beneficiário: Renata Nascimento Gomes
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
• Beneficiário: Hugo Aguirre Armelin
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 18/10937-3 - Cálulas satélite: efeitos da lipocalina, hemolina e peptídeos derivados, na proliferação e diferenciação de células quiescentes de músculo esquelético
• Beneficiário: Angela María Alvarez Gómez
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/50040-4 - Rational approach for searching molecular targets involved in inflammatory events and cell survival
• Beneficiário: Ana Marisa Chudzinski-Tavassi
• Modalidade de apoio: Auxílio à Pesquisa - Programa Centros de Pesquisa Aplicada