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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2017

Open Access 01-12-2017 | Research

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

Authors: Tomoko Hirakawa, Kaei Nasu, Yoko Aoyagi, Kanetoshi Takebayashi, Hisashi Narahara

Published in: Reproductive Biology and Endocrinology | Issue 1/2017

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.
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Metadata
Title
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
Authors
Tomoko Hirakawa
Kaei Nasu
Yoko Aoyagi
Kanetoshi Takebayashi
Hisashi Narahara
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2017
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-017-0272-3

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