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Turpin, B., Miller, W., Rosenfeldt, L., Kombrinck, K., Flick, M.J., Steinbrecher, K.A., Harmel-Laws, E., Mullins, E.S., Shaw, M., Witte, D.P., Revenko, A., Monia, B. And Palumbo, J.S. (2014) Thrombin Drives Tumorigenesis in Colitis-Associated Colon Cancer. Cancer Research, 74, 3020-3030.
https://doi.org/10.1158/0008-5472.CAN-13-3276

has been cited by the following article:

• TITLE: Partial Characterization of Thrombin Inhibitor(s) Derived from Salivary Glands of the Tick, Hyalomma dromedarii, and Related Anti-Cancer Potential

  AUTHORS: Wessam S. Ibrahim, Fatma S. A. Mohamed, Walaa A. Moselhy, Emtithal M. Abdel Samie, Aly Fahmy Mohamed

  KEYWORDS: Hyalomma dromedarii, Salivary Glands, Thrombin Inhibitor, Apoptosis, VEGF

  JOURNAL NAME: Advances in Entomology, Vol.9 No.1, December 1, 2020

  ABSTRACT: A long-term blood feeder, like the Hyalommadromedariitick, requires extended control over all hemostatic defense mechanisms generated by the host during feeding, including blood coagulation. To overcome this, ticks have evolved numerous molecules that target proteases in the blood coagulation cascade. New insights into the role of clotting factors in the development and progression of cancer have identified anticoagulant treatment as a potential therapeutic approach. In this context, the present work assessed the anticoagulation activities of crude and fractionated salivary gland extract (SGE) prepared from semi-fed H. dromedariifemales. Additionally, the antitumor effects of the potent anti-thrombin fractions were determined against colon cancer (Caco-2) and normal skin (HFB4) cells. Crude SGE significantly prolonged clotting time in prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT) assays and inhibited thrombin in FII-activity assay. Using anion-exchange chromatography, the fractions that strongly inhibited thrombin (3.A4 and 3.A5) were eluted. Both fractions prolonged the aPTT and TT clotting times and reduced the activity of FII significantly. The protein profiles of both fractions indicated the presence of a single polypeptide band of about 99 kDa. Regarding anti-cancer potential of the tested fractions, Caco-2 cells showed reduced viability with obvious morphological changes, induced apoptosis and a reduced level of vascular endothelial growth factor (VEGF). G2/M cell cycle arrest was observed only in 3.A5-treatedcells. No cytotoxic effects were observed in HFB4 cells. These results demonstrated the potential of tick-derived anticoagulants, specifically thrombin inhibitors, as effective tools in colorectal cancer treatment. Further purification of the effector molecule(s) is required to fully characterize their structures and mechanisms of action.