Targeting the integrin beta 1-focal adhesion kinase axis with artemisinin: Biophysical disruption of cell adhesion, migration, and invasion in tongue cancer

Abstract

Tongue cancer is a significant threat to human health due to its propensity to spread throughout the oral cavity and to other regions of the head and neck. The challenges posed by its high invasion, metastasis, and late clinical detection underscore the urgency for effective clinical interventions. In this study, we elucidate the promising anti-cancer properties of artemisinin, an anti-malarial drug, in inhibiting cellular interactions within a tongue cancer cell line. Our findings reveal that artemisinin treatment effectively suppresses phosphorylated focal adhesion kinase and its downstream AKT pathway, thereby enhancing apoptotic processes and inducing cell cycle arrest, consequently impeding cellular proliferation. Moreover, artemisinin treatment induces focal adhesion rearrangement and diminishes the cell's capacity to generate traction stress, consequently restraining cell migration on the matrix, as determined via traction force microscopy. Additionally, a transition from N-cadherin to E-cadherin expression occurs at cellular junctions, lowering intracellular stress, as measured by monolayer stress microscopy. This transition significantly curtails cellular migratory capabilities. Our in vivo studies corroborate these findings, showing a significant reduction in tumor volume following artemisinin treatment. Our study highlights the therapeutic potential of artemisinin use as a novel strategy for tongue cancer treatment, which acts via modulating both intracellular and intercellular interactions.