Anticancer effects of tangeretin associated with reactive oxygen species generation, mitochondrial dysfunction and apoptosis in CaSki cells

Abstract

Cervical cancer is the fourth most common cancer and the fourth leading cause of cancer-related mortality among women worldwide. Tangeretin (TAN), a polymethoxylated flavonoid derived from citrus fruit peel, exhibits relatively high structural stability due to its methoxy groups and exerts anticancer effects in various malignancies, including lung, liver and breast cancer. However, to the best of our knowledge, the anticancer effects of TAN in cervical cancer remain insufficiently explored. The present study investigated the mechanisms underlying the anticancer effects of TAN on the CaSki cervical cancer cell line. Cell viability was evaluated using the EZ-Cytox cell viability assay. The colony formation and cell cycle arrest assays demonstrated that TAN inhibited cell proliferation by inducing G1 phase arrest. The wound-healing and Transwell migration assays demonstrated that TAN could reduce the migratory ability of CaSki cells, and the Annexin V/propidium iodide staining assay revealed that TAN increased the apoptotic cell population. Mitochondrial reactive oxygen species (ROS) were identified using MitoSOX™ staining and the mitochondrial membrane potential (MMP) was detected using JC-1 staining. The findings of these assays suggested that TAN could increase mitochondrial ROS levels and decrease mitochondrial MMP in CaSki cells. Western blot analysis showed that TAN upregulated the protein expression levels of E-cadherin and Bax. In addition, TAN restored the tumor suppressor protein p53. Collectively, these findings suggested that may exhibit anticancer activity in CaSki cells.