Antrodia salmonea Extracts Regulate p53-AR Signaling and Apoptosis in Human Prostate Cancer LNCaP Cells
Antrodia salmonea (AS) is a genus of Antrodia, an epiphyte of Cunninghamia konishii in Taiwan. AS has been reported to have potential therapeutic effects on different diseases, including diarrhea, abdominal pain, and hypertension. AS has been reported to have anticancer effects on numerous cancer ty...
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creator | Chen, Chieh-Yin Li, Yu-Hsuan Liao, Wan-Ling Oner, Muhammet Cheng, Yu-Chiao Liu, Fang-Ling Cheng, Pang-Ting Celik, Ayse Wu, Jyh-Horng Lai, Chih-Ho Hsieh, Jer-Tsong Lin, Ho Chang, Ting-Chieh Chang, Chih-Ying Chen, Mei-Chih |
description | Antrodia salmonea (AS) is a genus of Antrodia, an epiphyte of Cunninghamia konishii in Taiwan. AS has been reported to have potential therapeutic effects on different diseases, including diarrhea, abdominal pain, and hypertension. AS has been reported to have anticancer effects on numerous cancer types, such as ovarian carcinoma and triple-negative breast cancer. Our previous studies demonstrated that antrocins and triterpenoids are possibly bioactive compositions. However, the effects of AS on prostate cancer remain unknown. Therefore, we investigated the role of AS in prostate cancer growth, apoptosis, and cell cycle regulation. The results showed that AS extracts significantly inhibited the proliferation of prostate cancer LNCaP cells in a dose-dependent manner and increased the levels of apoptotic markers (cleaved PARP and cleaved caspase 3/8/9). In addition, the cell cycle-related proteins CDK1, CDK2, CDK4, and their respective specific regulators Cyclin B1, Cyclin A, and Cyclin D were also affected. Besides, AS treatment increased p53 protein levels and slowed its degradation in LNCaP cells. Interestingly, we found that AS treatment reduced both total protein and Ser-81 phosphorylation levels of the androgen receptor (AR). Notably, the increase of nuclear p53 was accompanied by the down-regulation of AR, suggesting a reverse regulation between p53 and AR in LNCaP cells was triggered by AS treatment. These findings suggest that AS extracts trigger the apoptosis of prostate cancer cells through the reverse regulation of p53 and AR and elucidate that AS extracts might be a potential treatment for androgen-dependent prostate cancer in the near future. |
doi_str_mv | 10.1155/2022/7033127 |
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AS has been reported to have potential therapeutic effects on different diseases, including diarrhea, abdominal pain, and hypertension. AS has been reported to have anticancer effects on numerous cancer types, such as ovarian carcinoma and triple-negative breast cancer. Our previous studies demonstrated that antrocins and triterpenoids are possibly bioactive compositions. However, the effects of AS on prostate cancer remain unknown. Therefore, we investigated the role of AS in prostate cancer growth, apoptosis, and cell cycle regulation. The results showed that AS extracts significantly inhibited the proliferation of prostate cancer LNCaP cells in a dose-dependent manner and increased the levels of apoptotic markers (cleaved PARP and cleaved caspase 3/8/9). In addition, the cell cycle-related proteins CDK1, CDK2, CDK4, and their respective specific regulators Cyclin B1, Cyclin A, and Cyclin D were also affected. Besides, AS treatment increased p53 protein levels and slowed its degradation in LNCaP cells. Interestingly, we found that AS treatment reduced both total protein and Ser-81 phosphorylation levels of the androgen receptor (AR). Notably, the increase of nuclear p53 was accompanied by the down-regulation of AR, suggesting a reverse regulation between p53 and AR in LNCaP cells was triggered by AS treatment. These findings suggest that AS extracts trigger the apoptosis of prostate cancer cells through the reverse regulation of p53 and AR and elucidate that AS extracts might be a potential treatment for androgen-dependent prostate cancer in the near future.</description><identifier>ISSN: 1741-427X</identifier><identifier>EISSN: 1741-4288</identifier><identifier>DOI: 10.1155/2022/7033127</identifier><identifier>PMID: 36482936</identifier><language>eng</language><publisher>United States: Hindawi</publisher><subject>Androgen receptors ; Androgens ; Antibodies ; Antifungal agents ; Antrodia ; Apoptosis ; Biological activity ; Breast cancer ; Caspase-3 ; Cell cycle ; Cell growth ; Cell proliferation ; Cyclin A ; Cyclin B1 ; Cyclin D ; Cyclin-dependent kinases ; Diarrhea ; Down-regulation ; Kinases ; Life sciences ; Ligands ; Ovarian cancer ; Ovarian carcinoma ; p53 Protein ; Phosphorylation ; Poly(ADP-ribose) polymerase ; Prostate cancer ; Protein expression ; Protein synthesis ; Proteins ; Triterpenoids</subject><ispartof>Evidence-based complementary and alternative medicine, 2022, Vol.2022, p.7033127-12</ispartof><rights>Copyright © 2022 Chieh-Yin Chen et al.</rights><rights>Copyright © 2022 Chieh-Yin Chen et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2022 Chieh-Yin Chen et al. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c448t-662efdc5345303f3f4e4d4ecf96d5d2e6070d0172d382df2ac2a26af906fc4683</citedby><cites>FETCH-LOGICAL-c448t-662efdc5345303f3f4e4d4ecf96d5d2e6070d0172d382df2ac2a26af906fc4683</cites><orcidid>0000-0001-7849-9137 ; 0000-0002-3814-6916 ; 0000-0002-8934-1236</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9726253/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9726253/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,4010,27902,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36482936$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Muniyan, Sakthivel</contributor><contributor>Sakthivel Muniyan</contributor><creatorcontrib>Chen, Chieh-Yin</creatorcontrib><creatorcontrib>Li, Yu-Hsuan</creatorcontrib><creatorcontrib>Liao, Wan-Ling</creatorcontrib><creatorcontrib>Oner, Muhammet</creatorcontrib><creatorcontrib>Cheng, Yu-Chiao</creatorcontrib><creatorcontrib>Liu, Fang-Ling</creatorcontrib><creatorcontrib>Cheng, Pang-Ting</creatorcontrib><creatorcontrib>Celik, Ayse</creatorcontrib><creatorcontrib>Wu, Jyh-Horng</creatorcontrib><creatorcontrib>Lai, Chih-Ho</creatorcontrib><creatorcontrib>Hsieh, Jer-Tsong</creatorcontrib><creatorcontrib>Lin, Ho</creatorcontrib><creatorcontrib>Chang, Ting-Chieh</creatorcontrib><creatorcontrib>Chang, Chih-Ying</creatorcontrib><creatorcontrib>Chen, Mei-Chih</creatorcontrib><title>Antrodia salmonea Extracts Regulate p53-AR Signaling and Apoptosis in Human Prostate Cancer LNCaP Cells</title><title>Evidence-based complementary and alternative medicine</title><addtitle>Evid Based Complement Alternat Med</addtitle><description>Antrodia salmonea (AS) is a genus of Antrodia, an epiphyte of Cunninghamia konishii in Taiwan. AS has been reported to have potential therapeutic effects on different diseases, including diarrhea, abdominal pain, and hypertension. AS has been reported to have anticancer effects on numerous cancer types, such as ovarian carcinoma and triple-negative breast cancer. Our previous studies demonstrated that antrocins and triterpenoids are possibly bioactive compositions. However, the effects of AS on prostate cancer remain unknown. Therefore, we investigated the role of AS in prostate cancer growth, apoptosis, and cell cycle regulation. The results showed that AS extracts significantly inhibited the proliferation of prostate cancer LNCaP cells in a dose-dependent manner and increased the levels of apoptotic markers (cleaved PARP and cleaved caspase 3/8/9). In addition, the cell cycle-related proteins CDK1, CDK2, CDK4, and their respective specific regulators Cyclin B1, Cyclin A, and Cyclin D were also affected. Besides, AS treatment increased p53 protein levels and slowed its degradation in LNCaP cells. Interestingly, we found that AS treatment reduced both total protein and Ser-81 phosphorylation levels of the androgen receptor (AR). Notably, the increase of nuclear p53 was accompanied by the down-regulation of AR, suggesting a reverse regulation between p53 and AR in LNCaP cells was triggered by AS treatment. These findings suggest that AS extracts trigger the apoptosis of prostate cancer cells through the reverse regulation of p53 and AR and elucidate that AS extracts might be a potential treatment for androgen-dependent prostate cancer in the near future.</description><subject>Androgen receptors</subject><subject>Androgens</subject><subject>Antibodies</subject><subject>Antifungal agents</subject><subject>Antrodia</subject><subject>Apoptosis</subject><subject>Biological activity</subject><subject>Breast cancer</subject><subject>Caspase-3</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cell proliferation</subject><subject>Cyclin A</subject><subject>Cyclin B1</subject><subject>Cyclin D</subject><subject>Cyclin-dependent kinases</subject><subject>Diarrhea</subject><subject>Down-regulation</subject><subject>Kinases</subject><subject>Life sciences</subject><subject>Ligands</subject><subject>Ovarian cancer</subject><subject>Ovarian carcinoma</subject><subject>p53 Protein</subject><subject>Phosphorylation</subject><subject>Poly(ADP-ribose) polymerase</subject><subject>Prostate cancer</subject><subject>Protein expression</subject><subject>Protein 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salmonea Extracts Regulate p53-AR Signaling and Apoptosis in Human Prostate Cancer LNCaP Cells</title><author>Chen, Chieh-Yin ; Li, Yu-Hsuan ; Liao, Wan-Ling ; Oner, Muhammet ; Cheng, Yu-Chiao ; Liu, Fang-Ling ; Cheng, Pang-Ting ; Celik, Ayse ; Wu, Jyh-Horng ; Lai, Chih-Ho ; Hsieh, Jer-Tsong ; Lin, Ho ; Chang, Ting-Chieh ; Chang, Chih-Ying ; Chen, Mei-Chih</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c448t-662efdc5345303f3f4e4d4ecf96d5d2e6070d0172d382df2ac2a26af906fc4683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Androgen receptors</topic><topic>Androgens</topic><topic>Antibodies</topic><topic>Antifungal agents</topic><topic>Antrodia</topic><topic>Apoptosis</topic><topic>Biological activity</topic><topic>Breast cancer</topic><topic>Caspase-3</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Cell proliferation</topic><topic>Cyclin A</topic><topic>Cyclin B1</topic><topic>Cyclin D</topic><topic>Cyclin-dependent kinases</topic><topic>Diarrhea</topic><topic>Down-regulation</topic><topic>Kinases</topic><topic>Life sciences</topic><topic>Ligands</topic><topic>Ovarian cancer</topic><topic>Ovarian carcinoma</topic><topic>p53 Protein</topic><topic>Phosphorylation</topic><topic>Poly(ADP-ribose) polymerase</topic><topic>Prostate cancer</topic><topic>Protein expression</topic><topic>Protein synthesis</topic><topic>Proteins</topic><topic>Triterpenoids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Chieh-Yin</creatorcontrib><creatorcontrib>Li, Yu-Hsuan</creatorcontrib><creatorcontrib>Liao, Wan-Ling</creatorcontrib><creatorcontrib>Oner, Muhammet</creatorcontrib><creatorcontrib>Cheng, Yu-Chiao</creatorcontrib><creatorcontrib>Liu, Fang-Ling</creatorcontrib><creatorcontrib>Cheng, Pang-Ting</creatorcontrib><creatorcontrib>Celik, Ayse</creatorcontrib><creatorcontrib>Wu, 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Muhammet</au><au>Cheng, Yu-Chiao</au><au>Liu, Fang-Ling</au><au>Cheng, Pang-Ting</au><au>Celik, Ayse</au><au>Wu, Jyh-Horng</au><au>Lai, Chih-Ho</au><au>Hsieh, Jer-Tsong</au><au>Lin, Ho</au><au>Chang, Ting-Chieh</au><au>Chang, Chih-Ying</au><au>Chen, Mei-Chih</au><au>Muniyan, Sakthivel</au><au>Sakthivel Muniyan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antrodia salmonea Extracts Regulate p53-AR Signaling and Apoptosis in Human Prostate Cancer LNCaP Cells</atitle><jtitle>Evidence-based complementary and alternative medicine</jtitle><addtitle>Evid Based Complement Alternat Med</addtitle><date>2022</date><risdate>2022</risdate><volume>2022</volume><spage>7033127</spage><epage>12</epage><pages>7033127-12</pages><issn>1741-427X</issn><eissn>1741-4288</eissn><abstract>Antrodia salmonea (AS) is a genus of Antrodia, an epiphyte of Cunninghamia konishii in Taiwan. AS has been reported to have potential therapeutic effects on different diseases, including diarrhea, abdominal pain, and hypertension. AS has been reported to have anticancer effects on numerous cancer types, such as ovarian carcinoma and triple-negative breast cancer. Our previous studies demonstrated that antrocins and triterpenoids are possibly bioactive compositions. However, the effects of AS on prostate cancer remain unknown. Therefore, we investigated the role of AS in prostate cancer growth, apoptosis, and cell cycle regulation. The results showed that AS extracts significantly inhibited the proliferation of prostate cancer LNCaP cells in a dose-dependent manner and increased the levels of apoptotic markers (cleaved PARP and cleaved caspase 3/8/9). In addition, the cell cycle-related proteins CDK1, CDK2, CDK4, and their respective specific regulators Cyclin B1, Cyclin A, and Cyclin D were also affected. Besides, AS treatment increased p53 protein levels and slowed its degradation in LNCaP cells. Interestingly, we found that AS treatment reduced both total protein and Ser-81 phosphorylation levels of the androgen receptor (AR). Notably, the increase of nuclear p53 was accompanied by the down-regulation of AR, suggesting a reverse regulation between p53 and AR in LNCaP cells was triggered by AS treatment. These findings suggest that AS extracts trigger the apoptosis of prostate cancer cells through the reverse regulation of p53 and AR and elucidate that AS extracts might be a potential treatment for androgen-dependent prostate cancer in the near future.</abstract><cop>United States</cop><pub>Hindawi</pub><pmid>36482936</pmid><doi>10.1155/2022/7033127</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-7849-9137</orcidid><orcidid>https://orcid.org/0000-0002-3814-6916</orcidid><orcidid>https://orcid.org/0000-0002-8934-1236</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Androgen receptors Androgens Antibodies Antifungal agents Antrodia Apoptosis Biological activity Breast cancer Caspase-3 Cell cycle Cell growth Cell proliferation Cyclin A Cyclin B1 Cyclin D Cyclin-dependent kinases Diarrhea Down-regulation Kinases Life sciences Ligands Ovarian cancer Ovarian carcinoma p53 Protein Phosphorylation Poly(ADP-ribose) polymerase Prostate cancer Protein expression Protein synthesis Proteins Triterpenoids |
title | Antrodia salmonea Extracts Regulate p53-AR Signaling and Apoptosis in Human Prostate Cancer LNCaP Cells |
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