Astragalus membranaceus Extract Induces Apoptosis via Generation of Reactive Oxygen Species and Inhibition of Heat Shock Protein 27 and Androgen Receptor in Prostate Cancers

Sep 22, 2026

Although Astragalus membranaceus is recognized for anti-inflammatory, anti-obesity, and anti-oxidant activities, its apoptotic mechanism in prostate cancer has not been clarified. This study investigates apoptosis induced by a water extract from dried Astragalus membranaceus root (WAM) in prostate cancer cells through heat shock protein 27 (HSP27)/androgen receptor (AR) signaling. WAM increased cytotoxicity, sub-G1 cells, PARP and caspase-3 cleavage, reduced Bcl-2, and promoted TUNEL positivity. It lowered HSP27 Ser82 phosphorylation and inhibited AR and PSA expression by disrupting p-HSP27/AR binding, including in DHT-treated cells, and destabilized AR.

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CategoryHealthcare

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Article Astragalus membranaceus Extract Induces Apoptosis via Generation of Reactive Oxygen Species and Inhibition of Heat Shock Protein 27 and Androgen Receptor in Prostate Cancers Seok-Young Kim 1,†, Ji Eon Park 1,†, Hyo-Jung Lee 1, Deok Yong Sim 1, Chi-Hoon Ahn 1, Su-Yeon Park 1, Bum-Sang Shim 1, Bonglee Kim 1, Dae Young Lee 2 and Sung-Hoon Kim 1, * Citation: Kim, S.-Y.; Park, J.E.; Lee, H.-J.; Sim, D.Y.; Ahn, C.-H.; Park, S.-Y.; Shim, B.-S.; Kim, B.; Lee, D.Y.; Kim, S.-H. Astragalus membranaceus Extract Induces Apoptosis via Generation of Reactive Oxygen Species and Inhibition of Heat Shock Protein 27 and Androgen Receptor in Prostate Cancers. Int. J. Mol. Sci. 2024, 25, 2799 . [https://doi.org/10.3390/ijms25052799](https://doi.org/10.3390/ijms25052799) [Academic Editors: Ol](Academic Editors: Ol)ívia R. Pereira and Maria João Sousa Received: 8 December 2023 Revised: 31 January 2024 Accepted: 7 February 2024 Published: 28 February 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; [amabledaniel@naver.com](amabledaniel@naver.com) (S.-Y.K.); [wdnk77@naver.com](wdnk77@naver.com) (J.E.P.); [hyonice77@naver.com](hyonice77@naver.com) (H.-J.L.); [simdy0821@naver.com](simdy0821@naver.com) (D.Y.S.); [ach2565@naver.com](ach2565@naver.com) (C.-H.A.); [waterlilypark@naver.com](waterlilypark@naver.com) (S.-Y.P.); [eshimbs@khu.ac.kr](eshimbs@khu.ac.kr) (B.-S.S.); [bongleekim@khu.ac.kr](bongleekim@khu.ac.kr) (B.K.) 2 Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709, Republic of Korea; [dylee0809@gmail.com](dylee0809@gmail.com) * Correspondence: [sungkim7@khu.ac.kr](sungkim7@khu.ac.kr); Tel.: +82-2-961-9233 † These authors contributed equally to this work. Abstract: Although Astragalus membranaceus is known to have anti-inflammatory, anti-obesity, and anti-oxidant properties, the underlying apoptotic mechanism of Astragalus membranaceus extract has never been elucidated in prostate cancer. In this paper, the apoptotic mechanism of a water extract from the dried root of Astragalus membranaceus (WAM) was investigated in prostate cancer cells in association with heat shock protein 27 (HSP27)/androgen receptor (AR) signaling. WAMincreased cytotoxicity and the sub-G1 population, cleaved poly (ADP-ribose) polymerase (PARP) and cysteine aspartyl-specific protease 3 (caspase 3), and attenuated the expression of B-cell lymphoma 2 (Bcl-2) in LNCaP cells after 24 h of exposure. Consistently, WAM significantly increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive LNCaP cells. WAM decreased the phosphorylation of HSP27 on Ser82 and inhibited the expression of the AR and prostate-specific antigen (PSA), along with reducing the nuclear translocation of p-HSP27 and the AR via the disturbed binding of p-HSP27 with the AR in LNCaP cells. WAM consistently inhibited the expression of the AR and PSA in dihydrotestosterone (DHT)-treated LNCaP cells. WAM also suppressed AR stability, both in the presence and absence of cycloheximide, in LNCaP cells. Taken together, these findings provide evidence that WAM induces apoptosis via the inhibition of HSP27/AR signaling in prostate cancer cells and is a potent anticancer candidate for prostate cancer treatment. Keywords: apoptosis; AR; Astragalus membranaceus; HSP27; prostate cancer; ROS 1. Introduction Androgens and androgen receptor (AR) signaling play important roles in the normal prostate and prostate cancer (PCa) development, maintenance, and progression,

FAQs

What apoptotic process does WAM trigger in prostate cancer cells?

WAM increases cytotoxicity and sub-G1 population, activates apoptosis markers such as cleaved PARP and caspase 3, and elevates TUNEL-positive LNCaP cells.

How does WAM affect the HSP27/AR signaling pathway?

WAM decreases HSP27 phosphorylation at Ser82 and inhibits AR expression and PSA levels, including by disturbing binding between p-HSP27 and the AR and reducing nuclear translocation.

What evidence supports WAM as a potential anticancer candidate?

Together, the findings show WAM induces apoptosis via inhibition of HSP27/AR signaling and suppresses AR stability in LNCaP cells, supporting its potential as an anticancer candidate for prostate cancer treatment.

Sep 22, 2026

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