Non‐Anticoagulant Heparin: An In Vitro Investigation of a Novel Therapeutic Approach for Oral Cancer

ABSTRACT Background Oral squamous cell carcinoma (OSCC) represents a significant global oral health concern. Non‐anticoagulant heparin (NH) emerges as a promising solution considering the enhanced survival observed with anticoagulants in cancer treatment. Methods We used the MTS assay (0/24/48/72 h), scratch assay (MuviCyte, 0–18 h), invasion Matrigel (24 h), and cytotoxic assay (0–24 h) to assess the in vitro effects of NH and heparin (10, 20, 40, 80 U/mL) on three oral human cell lines (H400/H357/OKF6) as well as their ability to interfere with the chemotherapeutic agents 5FU and cisplatin (1–5 μg/mL). Results Remarkably, NH not only significantly induced a significant cytotoxic effect on both cancer cell lines at 80 U/mL but also inhibited proliferation at 48/72 h to a comparable extent as heparin. Notably, neither drug exhibited cytotoxic effects on the normal cells. Furthermore, in H400/H357 cells, both heparin and NH significantly inhibit the cell migration and invasion rate. Importantly, the combination of these drugs with commonly used chemotherapeutic agents for OSCC treatment did not compromise their efficacy against the tested cell lines. Conclusion NH demonstrates promising potential without compromising the efficacy of commonly used chemotherapeutic agents. These results underscore the need for the translation of this research to preclinical animal models.