Commonly Prescribed Anticoagulants Exert Anticancer Effects in Oral Squamous Cell Carcinoma Cells In Vitro

SIMPLE SUMMARY: Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide with 840,000 new cases and 420,000 deaths in 2020. Anticoagulants are widely prescribed medications routinely administered to help prevent blood clots. Despite the great relevance of these two topics, there is complete lack of knowledge regarding the potential effects that these drugs could exert on oral cancer patients. In this in vitro study, we comprehensively investigated the effect of anticoagulants on OSCC activity. This includes the effect of these drugs on cancer cell ability to survive, migrate to colonise distant sites, and resist treatment with conventional chemotherapy. We have demonstrated for the first time that various anticoagulants have anticancer effects on OSCC. Moreover, some of the anticoagulants tested were able to reduce the migratory ability of cancer cells. Finally, the great majority of anticoagulants studied reduced the effectiveness of the tested chemotherapeutic agent, allowing an increase in cancer cell proliferation. Our results highlight the need for urgent further research in the field, to improve the anticoagulant strategies in patients with oral cancer, and in turn their prognosis. ABSTRACT: Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. With anticoagulant usage on the rise, it is important to elucidate their potential effects on tumour biology and interactions with chemotherapeutics. The aim of the present study was to investigate the effects of anticoagulants on OSCC cell lines and their interactions with the drug 5-fluorouracil (5-FU). Cell proliferation was assessed using an MTS in vitro assay in two human OSCC cell lines (H357/H400) and in normal oral keratinocytes (OKF6) treated with the 5-FU (0.2/1/5/10 μg/mL), conventional anticoagulants warfarin (1/5/10/20 μM) and heparin (5/20/80 U), as well as four new oral anticoagulants, dabigatran (5/10/20 μM), rivaroxaban (5/10/20 μM), apixaban (0.1/1/5 μg/mL), and edoxaban (5/10/20 μM). Cell migration was assessed at 3 h intervals up to18 h using a wound healing assay. Our results clearly demonstrate, for the first time, that commonly prescribed anticoagulants exert in vitro antiproliferative effects on OSCC cells. Furthermore, treatment with some anticoagulants reduced the migration of OSCC cell lines. Nevertheless, most of the anticoagulants tested reduced the effectiveness of the chemotherapeutic agent tested, 5-FU, highlighting potential flaws in the current pharmacological management of these patients. Our findings showed the need for the immediate translation of this research to preclinical animal models.