Arcyriaflavin a, a cyclin D1-cyclin-dependent kinase4 inhibitor, induces apoptosis and inhibits proliferation of human endometriotic stromal cells: a potential therapeutic agent in endometriosis

• Published in: Reproductive biology and endocrinology 2017-07, Vol.15 (1), p.53-53, Article 53
• Main Authors: Hirakawa, Tomoko, Nasu, Kaei, Aoyagi, Yoko, Takebayashi, Kanetoshi, Narahara, Hisashi
• Format: Article
• Language: English
• Subjects: Angiogenesis; Apoptosis; Apoptosis - drug effects; Breast cancer; Carbazoles - pharmacology; Caspase; Caspases - metabolism; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell death; Cell growth; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Cells, Cultured; Cyclin D1; Cyclin D1 - metabolism; Cyclin D1 inhibitor; Cyclin-dependent kinase 4; Cyclin-Dependent Kinase 4 - antagonists & inhibitors; Cyclin-Dependent Kinase 4 - metabolism; Cyclin-dependent kinases; Drug therapy; Endometriosis; Endometriosis - drug therapy; Endometriosis - metabolism; Endometriosis - pathology; Enzyme-linked immunosorbent assay; Female; Flow cytometry; G1 phase; Gene expression; Genetic aspects; Health aspects; Humans; Kinases; Menstruation; MicroRNAs; miRNA; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - prevention & control; Pathogenesis; Physiological aspects; Protein kinases; Proteins; Stromal cells; Stromal Cells - drug effects; Stromal Cells - metabolism; Transfection; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 1477-7827; 1477-7827
• DOI: 10.1186/s12958-017-0272-3

We previously showed that microRNA-503 (miR-503) transfection into endometriotic cyst stromal cells (ECSCs) induced cell cycle arrest at the G0/G1 phase by suppressing cyclin D1. This finding prompted us to evaluate the potential therapeutic effects of cyclin D1 inhibitors in endometriotic cells. This study aimed to determine whether arcyriaflavin A, a representative inhibitor of cyclin D1-cyclin-dependent kinase 4 (CDK4), is beneficial in the treatment of endometriosis. ECSCs were isolated from the ovarian endometriotic tissues of 32 women. The effects of arcyriaflavin A on cell viability and proliferation, vascular endothelial growth factor A expression, apoptosis, and cell cycle progression were evaluated using a modified methylthiazoletetrazolium assay, enzyme-linked immunosorbent assay (ELISA), Caspase-Glo® 3/7 assay, and flow cytometry. Arcyriaflavin A significantly inhibited cell viability, proliferation, and angiogenesis of ECSCs as assessed using the 5-bromo-2-deoxyuridine (BrdU) and methylthiazoletetrazolium bromide (MTT) assays, and vascular endothelial growth factor (VEGF) ELISA. Arcyriaflavin A induced apoptosis as shown in the Caspase-Glo® 3/7 assay and cell death detection ELISA whilethe cell cycle was arrested at the G0/G1 phase. The findings indicate that cyclin D1-CDK4 inhibitors may be promising candidates for the treatment of endometriosis. This is the first study to demonstrate the potential usefulness of arcyriaflavin A as a therapeutic agent for endometriosis. Further studies of the effects of cyclin D1-CDK4 inhibitors on endometriosis may provide useful information on pathogenesis and treatment.