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Apigenin induces ROS‐dependent apoptosis and ER stress in human endometriosis cells
Author(s) -
Park Sunwoo,
Lim Whasun,
Bazer Fuller W.,
Song Gwonhwa
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26054
Subject(s) - apigenin , apoptosis , endoplasmic reticulum , unfolded protein response , reactive oxygen species , microbiology and biotechnology , oxidative stress , chemistry , cancer research , pharmacology , biology , biochemistry , flavonoid , antioxidant
Apigenin is a plant‐derived flavonoid having antiproliferative, anti‐inflammatory, and anti‐angiogenic properties in chronic and metabolic diseases, and cancers. However, the functional role of apigenin remains to be identified in human endometriosis that is a benign inflammatory disease causing infertility, dysmenorrhea, dyspareunia, and chronic abdominal or pelvic pain. In the present study, we determined the effects of apigenin on two well‐established human endometriosis cell lines (VK2/E6E7 and End1/E6E7). Apigenin reduced proliferation and induced cell cycle arrest and apoptosis in the both endometriosis cell lines. In addition, it disrupted mitochondrial membrane potential (MMP) which was accompanied by an increase in concentration of calcium ions in the cytosol and in pro‐apoptotic proteins including Bax and cytochrome c in the VK2/E6E7 and End1/E6E7 cells. Moreover, apigenin treated cells accumulated excessive reactive oxygen species (ROS), and experienced lipid peroxidation and endoplasmic reticulum (ER) stress with activation of the unfolded protein response (UPR) regulatory proteins. Furthermore, the apigenin‐induced apoptosis in endometriosis cells was regulated via the ERK1/2, JNK, and AKT cell signaling pathways. Taken together, apigenin is a potential novel therapeutic agent to overcome current limitations in the treatment to endometriosis.