In vitro evaluation of cannabidiol effects on cisplatin response in primary and metastatic human oral cancer cell models

Abstract

Abstract

Oral cancer remains one of the most aggressive and treatment-resistant malignancies in humans. Although cisplatin-based chemotherapy is a cornerstone of OC treatment, its effectiveness is often limited by the development of chemoresistance. Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa, has been shown to modulate multiple cellular pathways and enhance the efficacy of anticancer agents. Here, we evaluated the effects of CBD on cisplatin response and key cellular behaviors using primary (HN4) and metastatic (HN12) human oral cancer cell models. Cell viability, clonogenic growth, and migration were assessed following single or combined treatments. Notably, CBD markedly enhanced cisplatin-induced cytotoxicity, resulting in significant decreases in cell viability, clonogenic growth, and migration compared to treatment with cisplatin alone. These findings provide mechanistic insight into how CBD modulates cellular responses underlying cisplatin treatment. Overall, our results suggest that CBD could serve as an adjuvant to sensitize resistant tumors and mitigate aggressive tumor behaviors, warranting further investigation of its combination with conventional chemotherapy in oral cancer.

Keywords: Oral cancer. Cannabidiol CBD. Cisplatin. Chemoresistance. Primary and metastatic cell models.