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Emerging Therapeutic Activity of Davallia formosana on Prostate Cancer Cells through Coordinated Blockade of Lipogenesis and Androgen Receptor Expression

Background: Prostate cancer (PCa) is the most prevalent malignancy diagnosed in men in Western countries. There is currently no effective therapy for advanced PCa aggressiveness, including castration-resistant progression. The aim of this study is to evaluate the potential efficacy and determine the...

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Autores principales: Hsieh, Po-Fan, Jiang, Wen-Ping, Huang, Shih-Yin, Basavaraj, Praveenkumar, Wu, Jin-Bin, Ho, Hui-Ya, Huang, Guan-Jhong, Huang, Wen-Chin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226131/
https://www.ncbi.nlm.nih.gov/pubmed/32276528
http://dx.doi.org/10.3390/cancers12040914
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author Hsieh, Po-Fan
Jiang, Wen-Ping
Huang, Shih-Yin
Basavaraj, Praveenkumar
Wu, Jin-Bin
Ho, Hui-Ya
Huang, Guan-Jhong
Huang, Wen-Chin
author_facet Hsieh, Po-Fan
Jiang, Wen-Ping
Huang, Shih-Yin
Basavaraj, Praveenkumar
Wu, Jin-Bin
Ho, Hui-Ya
Huang, Guan-Jhong
Huang, Wen-Chin
author_sort Hsieh, Po-Fan
collection PubMed
description Background: Prostate cancer (PCa) is the most prevalent malignancy diagnosed in men in Western countries. There is currently no effective therapy for advanced PCa aggressiveness, including castration-resistant progression. The aim of this study is to evaluate the potential efficacy and determine the molecular basis of Davallia formosana (DF) in PCa. Methods: LNCaP (androgen-sensitive) and C4-2 (androgen-insensitive/castration-resistant) PCa cells were utilized in this study. An MTT-based method, a wound healing assay, and the transwell method were performed to evaluate cell proliferation, migration, and invasion. Intracellular fatty acid levels and lipid droplet accumulation were analyzed to determine lipogenesis. Moreover, apoptotic assays and in vivo experiments were conducted. Results: DF ethanol extract (DFE) suppressed proliferation, migration, and invasion in PCa cells. DFE attenuated lipogenesis through inhibition of the expression of sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FASN). Moreover, DFE decreased androgen receptor (AR) and prostate-specific antigen (PSA) expression in PCa cells. We further showed the potent therapeutic activity of DFE by repressing the growth and leading to apoptosis of subcutaneous C4-2 tumors in a xenograft mouse model. Conclusions: These data provide a new molecular basis of DFE in PCa cells, and co-targeting SREBP-1/FASN/lipogenesis and the AR axis by DFE could be employed as a novel and promising strategy for the treatment of PCa.
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spelling pubmed-72261312020-05-18 Emerging Therapeutic Activity of Davallia formosana on Prostate Cancer Cells through Coordinated Blockade of Lipogenesis and Androgen Receptor Expression Hsieh, Po-Fan Jiang, Wen-Ping Huang, Shih-Yin Basavaraj, Praveenkumar Wu, Jin-Bin Ho, Hui-Ya Huang, Guan-Jhong Huang, Wen-Chin Cancers (Basel) Article Background: Prostate cancer (PCa) is the most prevalent malignancy diagnosed in men in Western countries. There is currently no effective therapy for advanced PCa aggressiveness, including castration-resistant progression. The aim of this study is to evaluate the potential efficacy and determine the molecular basis of Davallia formosana (DF) in PCa. Methods: LNCaP (androgen-sensitive) and C4-2 (androgen-insensitive/castration-resistant) PCa cells were utilized in this study. An MTT-based method, a wound healing assay, and the transwell method were performed to evaluate cell proliferation, migration, and invasion. Intracellular fatty acid levels and lipid droplet accumulation were analyzed to determine lipogenesis. Moreover, apoptotic assays and in vivo experiments were conducted. Results: DF ethanol extract (DFE) suppressed proliferation, migration, and invasion in PCa cells. DFE attenuated lipogenesis through inhibition of the expression of sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FASN). Moreover, DFE decreased androgen receptor (AR) and prostate-specific antigen (PSA) expression in PCa cells. We further showed the potent therapeutic activity of DFE by repressing the growth and leading to apoptosis of subcutaneous C4-2 tumors in a xenograft mouse model. Conclusions: These data provide a new molecular basis of DFE in PCa cells, and co-targeting SREBP-1/FASN/lipogenesis and the AR axis by DFE could be employed as a novel and promising strategy for the treatment of PCa. MDPI 2020-04-08 /pmc/articles/PMC7226131/ /pubmed/32276528 http://dx.doi.org/10.3390/cancers12040914 Text en © 2020 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hsieh, Po-Fan
Jiang, Wen-Ping
Huang, Shih-Yin
Basavaraj, Praveenkumar
Wu, Jin-Bin
Ho, Hui-Ya
Huang, Guan-Jhong
Huang, Wen-Chin
Emerging Therapeutic Activity of Davallia formosana on Prostate Cancer Cells through Coordinated Blockade of Lipogenesis and Androgen Receptor Expression
title Emerging Therapeutic Activity of Davallia formosana on Prostate Cancer Cells through Coordinated Blockade of Lipogenesis and Androgen Receptor Expression
title_full Emerging Therapeutic Activity of Davallia formosana on Prostate Cancer Cells through Coordinated Blockade of Lipogenesis and Androgen Receptor Expression
title_fullStr Emerging Therapeutic Activity of Davallia formosana on Prostate Cancer Cells through Coordinated Blockade of Lipogenesis and Androgen Receptor Expression
title_full_unstemmed Emerging Therapeutic Activity of Davallia formosana on Prostate Cancer Cells through Coordinated Blockade of Lipogenesis and Androgen Receptor Expression
title_short Emerging Therapeutic Activity of Davallia formosana on Prostate Cancer Cells through Coordinated Blockade of Lipogenesis and Androgen Receptor Expression
title_sort emerging therapeutic activity of davallia formosana on prostate cancer cells through coordinated blockade of lipogenesis and androgen receptor expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226131/
https://www.ncbi.nlm.nih.gov/pubmed/32276528
http://dx.doi.org/10.3390/cancers12040914
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