Anticancer Effects of Tangeretin on Apoptosis Induction and Cell Growth Inhibition through Mediating Reactive Oxygen Species in Endometrial Cancer Cells

Endometrial cancer, the most common gynecologic malignancy, originates within the epithelial lining of the uterus. Although early diagnosis can lead to effective treatment and improved recovery rates, the worldwide incidence and mortality rates of this cancer continue to rise. The prognosis is particularly poor in cases of metastatic or recurrent disease. Tangeretin, a flavonoid found in citrus fruits, is known for its various biological properties, including antioxidant and anti-inflammatory activities. It has demonstrated anticancer effects against a range of cancers, including bladder, colorectal carcinoma, and breast cancer. However, its effects on endometrial cancer cells have not been previously examined. Here, we investigate the effects of tangeretin on cell viability, proliferation, migration, reactive oxygen species (ROS) generation, and apoptosis in Ishikawa cells, a well-characterized epithelial model used in endometrial research. Our results show that tangeretin treatment significantly inhibits the viability and proliferation of Ishikawa cells. In addition, it suppresses cell migration, as evidenced by wound healing assays. The 2',7'-dichlorofluorescein diacetate assay revealed that tangeretin enhances ROS generation. Moreover, an annexin V/propidium iodide assay confirmed that tangeretin induces apoptotic death in Ishikawa cells. The expression of B-cell lymphoma 2-associated X protein was analyzed to validate the induction of apoptosis. These findings suggest that tangeretin exhibits anticancer effects on endometrial cancer cells by inhibiting proliferation and migration while promoting apoptosis.