Rational development of a novel TFPI-like inhibitor from Amblyomma cajennense tick

Abstract

Hematophagous organisms have been described to possess specific blood coagulation inhibitors with different structures and novel mechanism of action. A factor Xa inhibitor was identified through the salivary glands transcriptome from the adult Amblyomma cajennense tick. The recombinant form was expressed in Escherichia coli and named Amblyomin-X. The recombinant protein not only inhibits factor X, but is also able to inhibit the activation of factor X by the extrinsic tenase complex. It seems to activate the apoptosis pathway through proteasome inhibition and endoplasmic reticulum-stress. It promotes regression and reduction of lung metastasis in murine melanoma tumor, and does not affect normal cells, emphasizing its selectivity of action.

• Amblyomma cajennense
• Amblyomin-X
• antitumor agent
• apoptosis
• Kunitz-type inhibitor
• TFPI-like inhibitor