Artesunate altered cellular mechanical properties leading to deregulation of cell proliferation and migration in esophageal squamous cell carcinoma.

ABSTRACT

Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer in China. Artesunate (ART) is used clinically as an anti-malarial agent and exhibits potent antiproliferative activity. In addition, ART has demonstrated remarkable antitumor activity, presenting a novel candidate for cancer chemotherapy. However, its effect on ESCC remains unknown. The present study analyzed the antitumor effects of ART in the KYSE-150 ESCC line by assessing cell proliferation, cell death, cell migration/invasion and the biomechanical properties of ART-treated KYSE-150 cells. ART treatment significantly suppressed the proliferation of KYSE-150 cells in a dose- and time-dependent manner, as assessed by MTT assay. Following treatment with 30 mg/l ART, the cell population in the G0/G1 phase and the level of cell apoptosis significantly increased from 54±1.5 to 68.1±0.3%, and from 4.53±0.58 to 12.45±0.62%, respectively. Furthermore, the cell migration and invasion of KYSE-150 cells treated with 30 mg/l ART was markedly inhibited. The cell membrane and biomechanical properties were investigated using atomic force microscopy, as targets of ART action. ESCC cells treated with 30 mg/l ART exhibited increased adhesive force, increased cytomembrane roughness and reduced elasticity compared with the control group (KYSE-150 cells without ART treatment). The biomechanical properties of KYSE-150 cells treated with 30 mg/l ART were similar to those of the SHEE normal human esophageal epithelial cell line. In conclusion, the present study demonstrated that ART may inhibit cell proliferation and migration in ESCC through changes in the biomechanical properties of the ESCC cells.