Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2021.045
Luteolin Promotes Apoptosis of Endometriotic Cells and Inhibits the Alternative Activation of Endometriosis-Associated Macrophages
Jeong-Hwa Woo1, Dae Sik Jang1,2,*, and Jung-Hye Choi1,2,*
1College of Pharmacy, Kyung Hee University, Seoul 02447,
2Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 02447, Republic of Korea
*E-mail: dsjang@khu.ac.kr (Jang DS), jchoi@khu.ac.kr (Choi JH)
Tel: +82-2-961-0719 (Jang DS), +82-2-961-2172 (Choi JH)
Fax: +82-2-961-9580 (Jang DS), +82-2-961-9580 (Choi JH)
Received: March 7, 2021; Revised: April 4, 2021; Accepted: April 19, 2021; Published online: May 20, 2021.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Luteolin, a flavonoid present in several fruits, vegetables, nuts, and herbs reportedly exhibits anti-cancer and anti-inflammatory properties. However, the effect of luteolin on endometriosis, a painful condition characterized by the ectopic growth of endometrial tissue and pelvic inflammation, remains elusive. Herein, we observed that luteolin inhibited cell growth and induced apoptosis of 12Z human endometriotic cells by activating caspase-3, -8, and -9. Additionally, luteolin significantly inhibited the expression of key chemokines, C-C motif chemokine ligand 2 (CCL2) and CCL5, required for monocyte/macrophage influx at endometriotic sites. In macrophages stimulated by endometriotic cells, luteolin treatment suppressed the intracellular expression of M2 markers and endometriosis-promoting factors. Collectively, our data suggest that luteolin exerts anti-endometriotic effects by stimulating endometriotic cell apoptosis and hindering the alternative activation of macrophages.
Keywords: Luteolin, Endometriosis, Macrophages, Apoptosis, M2 polarization


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