Artemisia leaf extract induces apoptosis in human endometriotic cells through regulation of the p38 and NFκB pathways

Abstract

Ethnopharmacological relevanceArtemisia leaves have long been used for the treatment of gynecological disorders, including infertility and dysmenorrhea, which can be commonly caused by endometriosis. In the present study, we investigated the effect of Artemisia princeps extract (APE) on the cell growth and apoptosis of human endometriotic cells. Materials and methodsMTT assays and FACS analysis using PI and Annexin staining were performed to study cell viability, cell cycle progression, and apoptosis. We also explored the mechanism of APE-induced effects by evaluating the activation of caspases, Akt, p38, and NFκB. The expressions of XIAP, Bcl-2, and Bcl-xL were measured by real-time RT-PCR and Western blot analyses. ResultsAPE significantly inhibited the cell viability of 11Z and 12Z human endometriotic epithelial cells. Interestingly, endometriotic cells were more sensitive to APE treatment than immortalized endometrial cells (HES). Treatment with APE induced apoptosis of 11Z cells in a time-dependent manner, as shown by accumulation of sub G1 and apoptotic cell populations. In addition, treatment with APE stimulated the activation of caspase -3, -8, and -9 in a dose- and time-dependent manner. Furthermore, p38 was activated by APE treatment, and the p38 inhibitor SB203580 markedly inhibited APE-induced cell death in 11Z cells. Moreover, treatment with APE suppressed the activation of NFκB and the expressions of anti-apoptotic factors such as XIAP, Bcl-2, and Bcl-xL. ConclusionThese results indicate that APE is a potential anti-endometriotic agent, acting to induce apoptosis of endometrial cells through the modulation of the p38 and NFκB pathways.