Abstract

Background: Available treatments for endometriosis remain unsatisfactory; therefore, there is an urgent demand for novel and effective therapeutic strategies.This study focused on the therapeutic effect of cepharanthine, a monomer derived from a Chinese herb, on endometriosis in vitro, in patient-derived eutopic endometrial organoids, and in vivo. Methods: Patient-derived ectopic endometrial stromal cells were isolated from ovarian endometriomas. Organoids were generated from the eutopic endometrium of patients with endometriosis. Ectopic endometrial stromal cells, eutopic endometrial organoids, and immortalized endometrial stromal cells were used to evaluate the effects of cepharanthine on cell viability, growth, and apoptosis. Female BALB/c mice were used to develop a peritoneal endometriosis model. Results: Cepharanthine treatment decreased the viability of immortalized endometrial stromal cells, patient-derived endometriotic stromal cells, as well as eutopic endometrial organoids. It induced DNA damage, downregulated cyclin D1, and caused cell-cycle arrest at the G0/G1 phase. It also promoted apoptosis by enhancing cytochrome C release, activating caspase-9 and caspase-3, increasing the expression of proapoptotic factor Bax, and decreasing the expression of antiapoptotic factor B-cell lymphoma 2 (Bcl-2). Intraperitoneal administration of cepharanthine significantly inhibited the growth of murine peritoneal endometriosis model. The treatment significantly downregulated the protein expression of cyclin D1 and DNA repair protein RAD51 (RAD51), and increased phosphorylated histone H2AX (γ-H2AX) expression in endometriosis lesions, indicating that it induced DNA damage and impaired DNA repair. Additionally, Ki-67 expression was significantly decreased, and apoptosis was markedly increased in the lesions. Conclusions: Our results indicate that cepharanthin may represent a promising treatment option for endometriosis