Cargando…
A Standardized Wedelia chinensis Extract Overcomes the Feedback Activation of HER2/3 Signaling upon Androgen-Ablation in Prostate Cancer
Crosstalk between the androgen receptor (AR) and other signaling pathways in prostate cancer (PCa) severely affects the therapeutic outcome of hormonal therapy. Although anti-androgen therapy prolongs overall survival in PCa patients, resistance rapidly develops and is often associated with increase...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641394/ https://www.ncbi.nlm.nih.gov/pubmed/29066975 http://dx.doi.org/10.3389/fphar.2017.00721 |
_version_ | 1783271216809771008 |
---|---|
author | Tsai, Chin-Hsien Tzeng, Sheue-Fen Hsieh, Shih-Chuan Tsai, Chia-Jui Yang, Yu-Chih Tsai, Mong-Hsun Hsiao, Pei-Wen |
author_facet | Tsai, Chin-Hsien Tzeng, Sheue-Fen Hsieh, Shih-Chuan Tsai, Chia-Jui Yang, Yu-Chih Tsai, Mong-Hsun Hsiao, Pei-Wen |
author_sort | Tsai, Chin-Hsien |
collection | PubMed |
description | Crosstalk between the androgen receptor (AR) and other signaling pathways in prostate cancer (PCa) severely affects the therapeutic outcome of hormonal therapy. Although anti-androgen therapy prolongs overall survival in PCa patients, resistance rapidly develops and is often associated with increased AR expression and upregulation of the HER2/3-AKT signaling pathway. However, single agent therapy targeting AR, HER2/3 or AKT usually fails due to the reciprocal feedback loop. Previously, we reported that wedelolactone, apigenin, and luteolin are the active compounds in Wedelia chinensis herbal extract, and act synergistically to inhibit the AR activity in PCa. Here, we further demonstrated that an herbal extract of W. chinensis (WCE) effectively disrupted the AR, HER2/3, and AKT signaling networks and therefore enhanced the therapeutic efficacy of androgen ablation in PCa. Furthermore, WCE remained effective in suppressing AR and HER2/3 signaling in an in vivo adapted castration-resistant PCa (CRPC) LNCaP cell model that was insensitive to androgen withdrawal and second-line antiandrogen, enzalutamide. This study provides preclinical evidence that the use of a defined, single plant-derived extract can augment the therapeutic efficacy of castration with significantly prolonged progression-free survival. These data also establish a solid basis for using WCE as a candidate agent in clinical studies. |
format | Online Article Text |
id | pubmed-5641394 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56413942017-10-24 A Standardized Wedelia chinensis Extract Overcomes the Feedback Activation of HER2/3 Signaling upon Androgen-Ablation in Prostate Cancer Tsai, Chin-Hsien Tzeng, Sheue-Fen Hsieh, Shih-Chuan Tsai, Chia-Jui Yang, Yu-Chih Tsai, Mong-Hsun Hsiao, Pei-Wen Front Pharmacol Pharmacology Crosstalk between the androgen receptor (AR) and other signaling pathways in prostate cancer (PCa) severely affects the therapeutic outcome of hormonal therapy. Although anti-androgen therapy prolongs overall survival in PCa patients, resistance rapidly develops and is often associated with increased AR expression and upregulation of the HER2/3-AKT signaling pathway. However, single agent therapy targeting AR, HER2/3 or AKT usually fails due to the reciprocal feedback loop. Previously, we reported that wedelolactone, apigenin, and luteolin are the active compounds in Wedelia chinensis herbal extract, and act synergistically to inhibit the AR activity in PCa. Here, we further demonstrated that an herbal extract of W. chinensis (WCE) effectively disrupted the AR, HER2/3, and AKT signaling networks and therefore enhanced the therapeutic efficacy of androgen ablation in PCa. Furthermore, WCE remained effective in suppressing AR and HER2/3 signaling in an in vivo adapted castration-resistant PCa (CRPC) LNCaP cell model that was insensitive to androgen withdrawal and second-line antiandrogen, enzalutamide. This study provides preclinical evidence that the use of a defined, single plant-derived extract can augment the therapeutic efficacy of castration with significantly prolonged progression-free survival. These data also establish a solid basis for using WCE as a candidate agent in clinical studies. Frontiers Media S.A. 2017-10-10 /pmc/articles/PMC5641394/ /pubmed/29066975 http://dx.doi.org/10.3389/fphar.2017.00721 Text en Copyright © 2017 Tsai, Tzeng, Hsieh, Tsai, Yang, Tsai and Hsiao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Tsai, Chin-Hsien Tzeng, Sheue-Fen Hsieh, Shih-Chuan Tsai, Chia-Jui Yang, Yu-Chih Tsai, Mong-Hsun Hsiao, Pei-Wen A Standardized Wedelia chinensis Extract Overcomes the Feedback Activation of HER2/3 Signaling upon Androgen-Ablation in Prostate Cancer |
title | A Standardized Wedelia chinensis Extract Overcomes the Feedback Activation of HER2/3 Signaling upon Androgen-Ablation in Prostate Cancer |
title_full | A Standardized Wedelia chinensis Extract Overcomes the Feedback Activation of HER2/3 Signaling upon Androgen-Ablation in Prostate Cancer |
title_fullStr | A Standardized Wedelia chinensis Extract Overcomes the Feedback Activation of HER2/3 Signaling upon Androgen-Ablation in Prostate Cancer |
title_full_unstemmed | A Standardized Wedelia chinensis Extract Overcomes the Feedback Activation of HER2/3 Signaling upon Androgen-Ablation in Prostate Cancer |
title_short | A Standardized Wedelia chinensis Extract Overcomes the Feedback Activation of HER2/3 Signaling upon Androgen-Ablation in Prostate Cancer |
title_sort | standardized wedelia chinensis extract overcomes the feedback activation of her2/3 signaling upon androgen-ablation in prostate cancer |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641394/ https://www.ncbi.nlm.nih.gov/pubmed/29066975 http://dx.doi.org/10.3389/fphar.2017.00721 |
work_keys_str_mv | AT tsaichinhsien astandardizedwedeliachinensisextractovercomesthefeedbackactivationofher23signalinguponandrogenablationinprostatecancer AT tzengsheuefen astandardizedwedeliachinensisextractovercomesthefeedbackactivationofher23signalinguponandrogenablationinprostatecancer AT hsiehshihchuan astandardizedwedeliachinensisextractovercomesthefeedbackactivationofher23signalinguponandrogenablationinprostatecancer AT tsaichiajui astandardizedwedeliachinensisextractovercomesthefeedbackactivationofher23signalinguponandrogenablationinprostatecancer AT yangyuchih astandardizedwedeliachinensisextractovercomesthefeedbackactivationofher23signalinguponandrogenablationinprostatecancer AT tsaimonghsun astandardizedwedeliachinensisextractovercomesthefeedbackactivationofher23signalinguponandrogenablationinprostatecancer AT hsiaopeiwen astandardizedwedeliachinensisextractovercomesthefeedbackactivationofher23signalinguponandrogenablationinprostatecancer AT tsaichinhsien standardizedwedeliachinensisextractovercomesthefeedbackactivationofher23signalinguponandrogenablationinprostatecancer AT tzengsheuefen standardizedwedeliachinensisextractovercomesthefeedbackactivationofher23signalinguponandrogenablationinprostatecancer AT hsiehshihchuan standardizedwedeliachinensisextractovercomesthefeedbackactivationofher23signalinguponandrogenablationinprostatecancer AT tsaichiajui standardizedwedeliachinensisextractovercomesthefeedbackactivationofher23signalinguponandrogenablationinprostatecancer AT yangyuchih standardizedwedeliachinensisextractovercomesthefeedbackactivationofher23signalinguponandrogenablationinprostatecancer AT tsaimonghsun standardizedwedeliachinensisextractovercomesthefeedbackactivationofher23signalinguponandrogenablationinprostatecancer AT hsiaopeiwen standardizedwedeliachinensisextractovercomesthefeedbackactivationofher23signalinguponandrogenablationinprostatecancer |