Tick salivary gland as potential natural source for the discovery of promising antitumor drug candidates

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• 作者：Ana Marisa Chudzinski-Tavassi^a ; ^{ana.chudzinski@butantan.gov.br" class="auth_mail" title="E-mail the corresponding author} ; Katia L.P. Morais^a ; ^b ; Má ; rio Thiego Fernandes Pacheco^a ; Kerly Fernanda Mesquita Pasqualoto^a ; Jean Gabriel de Souza^a ; ^b
• 关键词：TF ; tissue factor ; TFPI ; tissue factor pathway inhibitor ; EP ; electrostatic potential ; mTOR ; mammalian target of rapamycin ; ER stress ; reticulum endoplasmic stress ; ROS ; reactive oxygen species
• 刊名：Biomedicine & Pharmacotherapy
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：77
• 期：Complete
• 页码：14-19
• 全文大小：1358 K

文摘

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.