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Citrus Flavone Tangeretin Inhibits CRPC Cell Proliferation by Regulating Cx26, AKT, and AR Signaling

Prostate cancer (PCa) progression depends on the action of androgen receptors (AR). Therefore, preventing ligand-mediated activation of AR is the first-line treatment strategy for metastatic PCa. Androgen deprivation therapy (ADT) can inhibit ligand binding to AR and alleviate PCa progression initia...

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Autores principales: Zhang, Ningfang, Wu, Wenqi, Huang, Yapeng, An, Lingyue, He, Zhichan, Chang, Zhenglin, He, Zhaohui, Lai, Yongchang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803427/
https://www.ncbi.nlm.nih.gov/pubmed/35111229
http://dx.doi.org/10.1155/2022/6422500
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author Zhang, Ningfang
Wu, Wenqi
Huang, Yapeng
An, Lingyue
He, Zhichan
Chang, Zhenglin
He, Zhaohui
Lai, Yongchang
author_facet Zhang, Ningfang
Wu, Wenqi
Huang, Yapeng
An, Lingyue
He, Zhichan
Chang, Zhenglin
He, Zhaohui
Lai, Yongchang
author_sort Zhang, Ningfang
collection PubMed
description Prostate cancer (PCa) progression depends on the action of androgen receptors (AR). Therefore, preventing ligand-mediated activation of AR is the first-line treatment strategy for metastatic PCa. Androgen deprivation therapy (ADT) can inhibit ligand binding to AR and alleviate PCa progression initially. However, due to the adaptation of PCa and recovery of AR signaling, castration-resistant prostate cancer (CRPC) eventually develops. Exploring novel dietary compounds that can target AR signaling appears to be a viable alternative therapeutic option for CRPC. In the present study, compounds from the citrus fruits were focused upon, which contain various flavonoid ingredients. Key components contained within orange peel, which is frequently used in traditional Chinese medicine, and downstream targets were first analyzed using network pharmacology approach. Notably, it was found that tangeretin, an active ingredient from orange peel, can significantly inhibit CRPC cell (C4-2 and Du145 cells) proliferation and migration whilst also synergistically increasing the sensitivity of CRPC cells to anti-tumor drugs sorafenib or cisplatin. Tangeretin also significantly reduced AR and AKT expressions in C4-2 cells and signal transducer and activator of transcription 3 expression in the androgen-insensitive cell line Du145. In addition, tangeretin increased the expression of both connexin26 (Cx26) and gap junction function, which may mediate the bystander effects of cisplatin or sorafenib. Taken together, the present study revealed a novel molecular mechanism by which tangeretin may inhibit the proliferation of CRPC cells, by affecting the Cx26/AKT/AR pathway, to synergistically increase the sensitivity of CRPC cells to sorafenib and cisplatin.
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spelling pubmed-88034272022-02-01 Citrus Flavone Tangeretin Inhibits CRPC Cell Proliferation by Regulating Cx26, AKT, and AR Signaling Zhang, Ningfang Wu, Wenqi Huang, Yapeng An, Lingyue He, Zhichan Chang, Zhenglin He, Zhaohui Lai, Yongchang Evid Based Complement Alternat Med Research Article Prostate cancer (PCa) progression depends on the action of androgen receptors (AR). Therefore, preventing ligand-mediated activation of AR is the first-line treatment strategy for metastatic PCa. Androgen deprivation therapy (ADT) can inhibit ligand binding to AR and alleviate PCa progression initially. However, due to the adaptation of PCa and recovery of AR signaling, castration-resistant prostate cancer (CRPC) eventually develops. Exploring novel dietary compounds that can target AR signaling appears to be a viable alternative therapeutic option for CRPC. In the present study, compounds from the citrus fruits were focused upon, which contain various flavonoid ingredients. Key components contained within orange peel, which is frequently used in traditional Chinese medicine, and downstream targets were first analyzed using network pharmacology approach. Notably, it was found that tangeretin, an active ingredient from orange peel, can significantly inhibit CRPC cell (C4-2 and Du145 cells) proliferation and migration whilst also synergistically increasing the sensitivity of CRPC cells to anti-tumor drugs sorafenib or cisplatin. Tangeretin also significantly reduced AR and AKT expressions in C4-2 cells and signal transducer and activator of transcription 3 expression in the androgen-insensitive cell line Du145. In addition, tangeretin increased the expression of both connexin26 (Cx26) and gap junction function, which may mediate the bystander effects of cisplatin or sorafenib. Taken together, the present study revealed a novel molecular mechanism by which tangeretin may inhibit the proliferation of CRPC cells, by affecting the Cx26/AKT/AR pathway, to synergistically increase the sensitivity of CRPC cells to sorafenib and cisplatin. Hindawi 2022-01-24 /pmc/articles/PMC8803427/ /pubmed/35111229 http://dx.doi.org/10.1155/2022/6422500 Text en Copyright © 2022 Ningfang Zhang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhang, Ningfang
Wu, Wenqi
Huang, Yapeng
An, Lingyue
He, Zhichan
Chang, Zhenglin
He, Zhaohui
Lai, Yongchang
Citrus Flavone Tangeretin Inhibits CRPC Cell Proliferation by Regulating Cx26, AKT, and AR Signaling
title Citrus Flavone Tangeretin Inhibits CRPC Cell Proliferation by Regulating Cx26, AKT, and AR Signaling
title_full Citrus Flavone Tangeretin Inhibits CRPC Cell Proliferation by Regulating Cx26, AKT, and AR Signaling
title_fullStr Citrus Flavone Tangeretin Inhibits CRPC Cell Proliferation by Regulating Cx26, AKT, and AR Signaling
title_full_unstemmed Citrus Flavone Tangeretin Inhibits CRPC Cell Proliferation by Regulating Cx26, AKT, and AR Signaling
title_short Citrus Flavone Tangeretin Inhibits CRPC Cell Proliferation by Regulating Cx26, AKT, and AR Signaling
title_sort citrus flavone tangeretin inhibits crpc cell proliferation by regulating cx26, akt, and ar signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803427/
https://www.ncbi.nlm.nih.gov/pubmed/35111229
http://dx.doi.org/10.1155/2022/6422500
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