title: Tick salivary gland as potential natural source for the discovery of promising antitumor drug candidates.
abstract: Nowadays, the relationship between cancer blood coagulation is well established. Regarding biodiversity and bioprospection, the tick biology has become quite attractive natural source for coagulation inhibitors, since its saliva has a very rich variety of bioactive molecules. For instance, a Kunitz-type FXa inhibitor, named Amblyomin-X, was found through transcriptome of the salivary gland of the Amblyomma cajennense. tick. This TFPI-like inhibitor, after obtained as recombinant protein, has presented anticoagulant, antigionenic, and antitumor properties. Although its effects on blood coagulation could be relevant for antitumor effect, Amblyomin-X acts by non-hemostatic mechanisms, such as proteasome inhibition and autophagy inhibition. Notably, cytotoxicity was not observed on non-tumor cells treated with this protein, suggesting some selectivity for tumor cells. Considering the current efforts in order to develop effective anticancer therapies, the findings presented in this review strongly suggest Amblyomin-X as a promising novel antitumor drug candidate.
authors.affiliation: Biochemistry and Biophysics Laboratory, Butantan Institute, SP, Brazil. Electronic address: ana.chudzinski@butantan.gov.br.
authors.forename: Ana Marisa
authors.initials: AM
authors.lastname: Chudzinski-Tavassi
authors.affiliation: Biochemistry and Biophysics Laboratory, Butantan Institute, SP, Brazil; Department of Biochemistry, Federal University of São Paulo, SP, Brazil.
authors.forename: Katia L P
authors.initials: KL
authors.lastname: Morais
authors.affiliation: Biochemistry and Biophysics Laboratory, Butantan Institute, SP, Brazil.
authors.forename: Mário Thiego Fernandes
authors.initials: MT
authors.lastname: Pacheco
authors.affiliation: Biochemistry and Biophysics Laboratory, Butantan Institute, SP, Brazil.
authors.forename: Kerly Fernanda Mesquita
authors.initials: KF
authors.lastname: Pasqualoto
authors.affiliation: Biochemistry and Biophysics Laboratory, Butantan Institute, SP, Brazil; Department of Biochemistry, Federal University of São Paulo, SP, Brazil.
authors.forename: Jean Gabriel
authors.initials: JG
authors.lastname: de Souza
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D060829:Arthropod Proteins; D045744:Cell Line, Tumor; D065427:Factor Xa Inhibitors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D011994:Recombinant Proteins; D012471:Salivary Proteins and Peptides / Q000494:pharmacology*; D013987:Ticks
chemical_list: C559369:Amblyomin-X protein, Amblyomma cajennense; D000925:Anticoagulants; D000970:Antineoplastic Agents; D060829:Arthropod Proteins; D065427:Factor Xa Inhibitors; D011994:Recombinant Proteins; D012471:Salivary Proteins and Peptides
keywords: Amblyomin-X; Anticoagulant; Antitumor drug candidate; Autophagy inhibition; Proteasome inhibitor; TFPI-like