Chrysin induces cell death and inhibits migration and invasion in squamous cervical carcinoma using a three-dimensional cell culture model

Cervical cancer remains a leading cause of cancer-related mortality among women worldwide, despite treatment advances. The most common form is squamous cell cervical carcinoma, primarily associated with human papillomavirus (HPV) type 16. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid with promising anticancer properties both in vitro and in vivo. The aim of this study was to evaluate the antiproliferative, anti-migratory, and anti-invasive effects of chrysin on the SiHa human cervical cancer cell line (HPV-16-positive) using a 3D cell culture model with spheroids. Cell viability was assessed using the resazurin assay, while cytostatic effects were monitored by measuring spheroid size through imaging. Migration was evaluated with the spheroid migration assay. The expression of matrix metalloproteinase (MMP)-2, MMP-9, and vascular endothelial growth factor (VEGF) was quantified by immunoenzymatic assays. Chrysin treatment exhibited concentration-dependent cytotoxic and cytostatic effects, reducing cell proliferation and decreasing SiHa spheroid size. Additionally, chrysin inhibited cell migration and invasion, potentially reducing metastatic potential, primarily by decreasing the production of MMP-2 and VEGF. These findings suggest that chrysin has therapeutic potential for squamous cell cervical carcinoma and warrants further in vivo preclinical studies.