Chrysin leads to cell death in endometriosis by regulation of endoplasmic reticulum stress and cytosolic calcium level. Issue 3 (9th October 2018)

• Record Type: Journal Article
• Authors: Ryu, Soomin; Bazer, Fuller W.; Lim, Whasun; Song, Gwonhwa
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 3(2019:Mar.)
• Page Start: 2480
• Page End: 2490
• Publication Date: 2018-10-09
• Subjects: apoptosis -- chrysin -- endometriosis -- endoplasmic reticulum stress -- phosphoinositide 3‐kinase/AKT signal pathway; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.26770
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: Chrysin is a natural compound derived from honey, propolis, or passion flowers and has many functional roles, such as antiinflammatory and antiangiogenesis effects. Although endometriosis is a benign gynecological disease, there is a need to identify the pathology and develop a therapy for endometriosis. Elucidating the biological mechanism of chrysin on endometriosis will improve the understanding of endometriosis. In this study, we confirmed the apoptotic effects of chrysin in human endometriotic cells using End1/E6E7 (endocervix‐derived endometriotic cells) and VK2/E6E7 (vaginal mucosa‐derived epithelial endometriotic cells). The results showed that chrysin suppressed the proliferation of endometriosis and induced programmed cell death through changing the cell cycle proportion and increasing the cytosolic calcium level and generation of reactive oxygen species. In addition, chrysin activated endoplasmic reticulum (ER) stress by stimulating the unfolded protein response proteins, especially the 78‐kDa glucose‐regulated protein–PRKR‐like ER kinase (PERK)–eukaryotic translation initiation factor 2α (eIF2α) pathway in both endometriotic cell lines. Furthermore, chrysin inactivated the intracellular phosphoinositide 3‐kinase (PI3K)/protein kinase B (PKB, also known as AKT) signaling pathway in a dose‐dependent manner. Collectively, the results of this study indicated that chrysin induced programmed cell death by activating the ER stress response and inactivating the PI3K signaling pathways in human endometriotic cells. Abstract : In this study, chrysin increased programmed cell death in human End1/E6E7 and VK2/E6E7 cells by changing the cell cycle proportion, cytosolic calcium influx, and ROS production in a dose‐dependent manner. Collectively, chrysin induces apoptotic effects in human endometriotic cells and can be used as a potential novel therapeutic agent for the treatment of endometriosis.