Osthole enhances antitumor activity and irradiation sensitivity of cervical cancer cells by suppressing ATM/NF-κB signaling

Osthole (7-methoxy-8-isopentenoxycoumarin) is an O-methylated coumarin, originally extracted from Chinese herbal medicine. It has been demonstrated that osthole has antitumor effects in various cancer cells in vitro. The present study assessed the effects of osthole on the regulation of cervical cancer cell viability, apoptosis, and radiation sensitization. HeLa, SiHa, C-33A and CaSki cervical cancer cell lines were cultured and treated with osthole and/or irradiation and then subjected to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide cell viability, colony formation, apoptosis, acridine orange/ethidium bromide fluorescence staining, wound-healing, Transwell migration and invasion, immunofluorescence, Comet and western blot assays. The data showed that osthole dose-dependently reduced cervical cancer cell viability, proliferation, and migration and invasion, but induced apoptosis. At the protein level, osthole affected the expression of cervical cancer cell epithelial-mesenchymal transition markers, which showed that the expression of E-cadherin was increased, whereas that of vimentin was decreased. Osthole treatment also sensitized cervical cancer cells to irradiation, showing increased DNA damage as assessed by the Comet assay, and inhibited nuclear factor-κB signaling. In conclusion, osthole is an herbal agent that may offer potential for used as an adjuvant treatment for cervical cancer.