5,7-Dimethoxyflavone induces apoptotic cell death in human endometriosis cell lines by activating the endoplasmic reticulum stress pathway

Endometriosis is a reproductive disorder characterized by the dislocation of endometrial tissues. Approximately 5–20% of women at their reproductive age are diagnosed with endometriosis, which causes chronic pain and infertility. Here, we demonstrated that the bioactive flavonoid, 5,7-dimethoxyflavone (DMF), exhibited antiproliferative and apoptotic effects in VK2/E6E7 and End1/E6E7 cells which were established from vaginal and endocervical tissue taken from a premenopausal woman undergoing hysterectomy for endometriosis. DMF treatment significantly elevated DNA fragmentation resulting in apoptotic cell death in both cell lines. Furthermore, DMF induced loss of mitochondrial membrane potential, dysregulation of intracellular calcium level, and ROS production, which accelerate apoptosis. Additionally, DMF modulated the expression of the signaling molecules related to cell survival and endoplasmic reticulum stress in VK2/E6E7 and End1/E6E7 cells. Overall, DMF may ameliorate endometriosis and can be a potential alternative to hormonal and surgical therapy for endometriosis treatment.