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Patchouli alcohol inhibits GPBAR1-mediated cell proliferation, apoptosis, migration, and invasion in prostate cancer

BACKGROUND: G protein-coupled bile acid receptor 1 (GPBAR1) is a G protein-coupled receptor for bile acids, which is widely expressed in many human tissues. Patchouli alcohol (PA) has been shown to have an anti-cancer effect, including in prostate cancer (PCa). This study sought to confirm the regul...

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Autores principales: Cai, Jian, Zhao, Juan, Gao, Ping, Xia, Yuguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9732702/
https://www.ncbi.nlm.nih.gov/pubmed/36507482
http://dx.doi.org/10.21037/tau-22-667
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author Cai, Jian
Zhao, Juan
Gao, Ping
Xia, Yuguo
author_facet Cai, Jian
Zhao, Juan
Gao, Ping
Xia, Yuguo
author_sort Cai, Jian
collection PubMed
description BACKGROUND: G protein-coupled bile acid receptor 1 (GPBAR1) is a G protein-coupled receptor for bile acids, which is widely expressed in many human tissues. Patchouli alcohol (PA) has been shown to have an anti-cancer effect, including in prostate cancer (PCa). This study sought to confirm the regulatory mechanism of GPBAR1 in the anti-cancer activity of PA in PCa. METHODS: The SwissTargetPrediction website (Pro >0) was used to predict the target of PA. The UALCAN and The Cancer Genome Atlas-Prostate cohort was used to examine the differentially expressed genes and PCa recurrence. A gene set enrichment analysis (GSEA) was conducted to analyze the relationship between the expression of GPBAR1 and PCa proliferation, migration, and invasion. Cell proliferation, migration, and invasion were assessed by colony formation, 5-Ethynyl-2’-deoxyuridine staining, cell scratch assays, and Transwell invasion assays, respectively. A xenograft animal model was established to assess the effect of PA on tumor growth in vivo. GPBAR1 protein and apoptosis related protein expression was measured by western blot. RESULTS: GPBAR1 was a PA target predicted by the SwissTargetPrediction website. PA inhibited the expression of GPBAR1 in PCa cells in a time- and dose-dependent manner. The abnormal expression of GPBAR1 was related to cell proliferation, migration, and invasion. Additionally, GPBAR1 overexpression promoted the cell proliferation, migration, and invasion, and inhibited the apoptosis of PCa cells. GPBAR1 silencing inhibited the cell proliferation, migration, and invasion, and promoted the apoptosis of PCa cells. High expressions of GPBAR1 suppressed tumor growth in tumor-bearing mice. Further, GPBAR1 promoted the activation of nuclear factor kappa B (NF-κB) signaling, and PA regulated the malignant phenotypes of PCa cells via the NF-κB signaling pathway mediated by GPBAR1. CONCLUSIONS: GPBAR1 is a promising drug target of PA, and was shown to regulate the proliferation, apoptosis, migration, and invasion of PCa cells through GPBAR1/NF-κB inhibition.
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spelling pubmed-97327022022-12-10 Patchouli alcohol inhibits GPBAR1-mediated cell proliferation, apoptosis, migration, and invasion in prostate cancer Cai, Jian Zhao, Juan Gao, Ping Xia, Yuguo Transl Androl Urol Original Article BACKGROUND: G protein-coupled bile acid receptor 1 (GPBAR1) is a G protein-coupled receptor for bile acids, which is widely expressed in many human tissues. Patchouli alcohol (PA) has been shown to have an anti-cancer effect, including in prostate cancer (PCa). This study sought to confirm the regulatory mechanism of GPBAR1 in the anti-cancer activity of PA in PCa. METHODS: The SwissTargetPrediction website (Pro >0) was used to predict the target of PA. The UALCAN and The Cancer Genome Atlas-Prostate cohort was used to examine the differentially expressed genes and PCa recurrence. A gene set enrichment analysis (GSEA) was conducted to analyze the relationship between the expression of GPBAR1 and PCa proliferation, migration, and invasion. Cell proliferation, migration, and invasion were assessed by colony formation, 5-Ethynyl-2’-deoxyuridine staining, cell scratch assays, and Transwell invasion assays, respectively. A xenograft animal model was established to assess the effect of PA on tumor growth in vivo. GPBAR1 protein and apoptosis related protein expression was measured by western blot. RESULTS: GPBAR1 was a PA target predicted by the SwissTargetPrediction website. PA inhibited the expression of GPBAR1 in PCa cells in a time- and dose-dependent manner. The abnormal expression of GPBAR1 was related to cell proliferation, migration, and invasion. Additionally, GPBAR1 overexpression promoted the cell proliferation, migration, and invasion, and inhibited the apoptosis of PCa cells. GPBAR1 silencing inhibited the cell proliferation, migration, and invasion, and promoted the apoptosis of PCa cells. High expressions of GPBAR1 suppressed tumor growth in tumor-bearing mice. Further, GPBAR1 promoted the activation of nuclear factor kappa B (NF-κB) signaling, and PA regulated the malignant phenotypes of PCa cells via the NF-κB signaling pathway mediated by GPBAR1. CONCLUSIONS: GPBAR1 is a promising drug target of PA, and was shown to regulate the proliferation, apoptosis, migration, and invasion of PCa cells through GPBAR1/NF-κB inhibition. AME Publishing Company 2022-11 /pmc/articles/PMC9732702/ /pubmed/36507482 http://dx.doi.org/10.21037/tau-22-667 Text en 2022 Translational Andrology and Urology. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Cai, Jian
Zhao, Juan
Gao, Ping
Xia, Yuguo
Patchouli alcohol inhibits GPBAR1-mediated cell proliferation, apoptosis, migration, and invasion in prostate cancer
title Patchouli alcohol inhibits GPBAR1-mediated cell proliferation, apoptosis, migration, and invasion in prostate cancer
title_full Patchouli alcohol inhibits GPBAR1-mediated cell proliferation, apoptosis, migration, and invasion in prostate cancer
title_fullStr Patchouli alcohol inhibits GPBAR1-mediated cell proliferation, apoptosis, migration, and invasion in prostate cancer
title_full_unstemmed Patchouli alcohol inhibits GPBAR1-mediated cell proliferation, apoptosis, migration, and invasion in prostate cancer
title_short Patchouli alcohol inhibits GPBAR1-mediated cell proliferation, apoptosis, migration, and invasion in prostate cancer
title_sort patchouli alcohol inhibits gpbar1-mediated cell proliferation, apoptosis, migration, and invasion in prostate cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9732702/
https://www.ncbi.nlm.nih.gov/pubmed/36507482
http://dx.doi.org/10.21037/tau-22-667
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