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

Although <i>Astragalus membranaceus</i> is known to have anti-inflammatory, anti-obesity, and anti-oxidant properties, the underlying apoptotic mechanism of <i>Astragalus membranaceus</i> extract has never been elucidated in prostate cancer. In this paper, the apoptotic mecha...

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Main Authors: Seok-Young Kim, Ji Eon Park, Hyo-Jung Lee, Deok Yong Sim, Chi-Hoon Ahn, Su-Yeon Park, Bum-Sang Shim, Bonglee Kim, Dae Young Lee, Sung-Hoon Kim
Format: Article
Language:English
Published: MDPI AG 2024-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/25/5/2799
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author Seok-Young Kim
Ji Eon Park
Hyo-Jung Lee
Deok Yong Sim
Chi-Hoon Ahn
Su-Yeon Park
Bum-Sang Shim
Bonglee Kim
Dae Young Lee
Sung-Hoon Kim
author_facet Seok-Young Kim
Ji Eon Park
Hyo-Jung Lee
Deok Yong Sim
Chi-Hoon Ahn
Su-Yeon Park
Bum-Sang Shim
Bonglee Kim
Dae Young Lee
Sung-Hoon Kim
author_sort Seok-Young Kim
collection DOAJ
description Although <i>Astragalus membranaceus</i> is known to have anti-inflammatory, anti-obesity, and anti-oxidant properties, the underlying apoptotic mechanism of <i>Astragalus membranaceus</i> extract has never been elucidated in prostate cancer. In this paper, the apoptotic mechanism of a water extract from the dried root of <i>Astragalus membranaceus</i> (WAM) was investigated in prostate cancer cells in association with heat shock protein 27 (HSP27)/androgen receptor (AR) signaling. WAM increased 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.
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spelling doaj.art-32af449851cb4e7aa74dac6e7da359742024-03-12T16:46:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-02-01255279910.3390/ijms25052799<i>Astragalus membranaceus</i> Extract Induces Apoptosis via Generation of Reactive Oxygen Species and Inhibition of Heat Shock Protein 27 and Androgen Receptor in Prostate CancersSeok-Young Kim0Ji Eon Park1Hyo-Jung Lee2Deok Yong Sim3Chi-Hoon Ahn4Su-Yeon Park5Bum-Sang Shim6Bonglee Kim7Dae Young Lee8Sung-Hoon Kim9College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaCollege of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaCollege of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaCollege of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaCollege of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaCollege of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaCollege of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaCollege of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Herbal Crop Research, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709, Republic of KoreaCollege of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaAlthough <i>Astragalus membranaceus</i> is known to have anti-inflammatory, anti-obesity, and anti-oxidant properties, the underlying apoptotic mechanism of <i>Astragalus membranaceus</i> extract has never been elucidated in prostate cancer. In this paper, the apoptotic mechanism of a water extract from the dried root of <i>Astragalus membranaceus</i> (WAM) was investigated in prostate cancer cells in association with heat shock protein 27 (HSP27)/androgen receptor (AR) signaling. WAM increased 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.https://www.mdpi.com/1422-0067/25/5/2799apoptosisAR<i>Astragalus membranaceus</i>HSP27prostate cancerROS
spellingShingle Seok-Young Kim
Ji Eon Park
Hyo-Jung Lee
Deok Yong Sim
Chi-Hoon Ahn
Su-Yeon Park
Bum-Sang Shim
Bonglee Kim
Dae Young Lee
Sung-Hoon Kim
<i>Astragalus membranaceus</i> Extract Induces Apoptosis via Generation of Reactive Oxygen Species and Inhibition of Heat Shock Protein 27 and Androgen Receptor in Prostate Cancers
International Journal of Molecular Sciences
apoptosis
AR
<i>Astragalus membranaceus</i>
HSP27
prostate cancer
ROS
title <i>Astragalus membranaceus</i> Extract Induces Apoptosis via Generation of Reactive Oxygen Species and Inhibition of Heat Shock Protein 27 and Androgen Receptor in Prostate Cancers
title_full <i>Astragalus membranaceus</i> Extract Induces Apoptosis via Generation of Reactive Oxygen Species and Inhibition of Heat Shock Protein 27 and Androgen Receptor in Prostate Cancers
title_fullStr <i>Astragalus membranaceus</i> Extract Induces Apoptosis via Generation of Reactive Oxygen Species and Inhibition of Heat Shock Protein 27 and Androgen Receptor in Prostate Cancers
title_full_unstemmed <i>Astragalus membranaceus</i> Extract Induces Apoptosis via Generation of Reactive Oxygen Species and Inhibition of Heat Shock Protein 27 and Androgen Receptor in Prostate Cancers
title_short <i>Astragalus membranaceus</i> Extract Induces Apoptosis via Generation of Reactive Oxygen Species and Inhibition of Heat Shock Protein 27 and Androgen Receptor in Prostate Cancers
title_sort i astragalus membranaceus i extract induces apoptosis via generation of reactive oxygen species and inhibition of heat shock protein 27 and androgen receptor in prostate cancers
topic apoptosis
AR
<i>Astragalus membranaceus</i>
HSP27
prostate cancer
ROS
url https://www.mdpi.com/1422-0067/25/5/2799
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