Apigenin Enhances the Radiosensitivity of TNBC Cells by Improving cGAS-STING Pathway Activity.

Abstract

Apigenin inhibits proliferation and induces apoptosis in triple-negative breast cancer (TNBC) cells, processes linked to DNA damage. However, the combined effect of apigenin and radiation on TNBC cells remains unclear. This study aimed to determine whether apigenin enhances the radiosensitivity of TNBC cells by activating the cGAS-STING pathway. Human TNBC cell lines MDA-MB-231 and MDA-MB-468 were X-ray irradiated, and the optimal apigenin concentration was determined by CCK-8 assay. Protein expression was analyzed by western blot, and cGAS or STING was knocked down using siRNA. DNA damage was assessed by immunofluorescence quantification of γH2AX and cytoplasmic dsDNA foci, while apoptosis was measured by flow cytometry. At 15 μM, apigenin showed minimal toxicity and enhanced radiosensitivity in both cell lines. Ionizing radiation increased cytosolic dsDNA levels and micronuclei formation, which was associated with upregulated cGAS-STING-TBK1-IRF3 pathway activity. Apigenin further enhanced this pathway by increasing radiation-induced cytosolic dsDNA and micronuclei, thereby promoting TNBC cell apoptosis. Moreover, knockdown of cGAS or STING significantly attenuated the apoptotic response induced by the combination of apigenin and radiation. These findings suggest that apigenin enhances the radiosensitivity of TNBC cells by activating the tumor cell-intrinsic cGAS-STING pathway.