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Athyrium multidentatum (Doll.) Ching extract induce apoptosis via mitochondrial dysfunction and oxidative stress in HepG2 cells
Athyrium multidentatum (Doll.) Ching (AMC), a unique and nutritious potherb widely distributed in china, has been extensively used in traditional Chinese medicine. Previous studies indicated that AMC extract exhibited antioxidant and antitumor properties. However, the chemical composition of AMC and...
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| Published in: | Scientific reports 2017-05, Vol.7 (1), p.2275-14, Article 2275 |
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| creator | Qi, Guoyuan Liu, Zhigang Fan, Rong Yin, Ziru Mi, Yashi Ren, Bo Liu, Xuebo |
| description | Athyrium multidentatum
(Doll.) Ching (AMC), a unique and nutritious potherb widely distributed in china, has been extensively used in traditional Chinese medicine. Previous studies indicated that AMC extract exhibited antioxidant and antitumor properties. However, the chemical composition of AMC and molecular mechanism of AMC toxicity to HepG2 cells have not yet been elucidated. Hence, this study aimed to investigate the chemical compositions and the underlying mechanisms of the antiproliferative and apoptotic effects of AMC on HepG2. HPLC-MS analysis showed that AMC contain five compounds with chlorogenic acid accounting for 43 percent. Also, AMC strongly inhibited the cell growth and induced apoptosis and cell cycle arrest in HepG2 cells by significantly upregulating the protein expressions of Fas, Fas-L, Bax/Bcl-2, cyto-
c
, cleaved caspase-3, and PARP in a dose-dependent manner, which indicates AMC induces apoptosis in HepG2 cells through both intrinsic and extrinsic pathways. Moreover, AMC provoked the production of ROS, H
2
O
2
, and NO, modulating the PI3K/Akt, MAPK, NFκB and Nrf2 pathways and their downstream transcriptional cascades, ultimately evoked oxidative stress and apoptosis in HpeG2 cells. Further
in vivo
experiments demonstrated that AMC significantly suppressed the tumor growth, suggesting that AMC may be a novel promising agent for hepatocellular carcinoma treatment. |
| doi_str_mv | 10.1038/s41598-017-02573-8 |
| format | article |
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(Doll.) Ching (AMC), a unique and nutritious potherb widely distributed in china, has been extensively used in traditional Chinese medicine. Previous studies indicated that AMC extract exhibited antioxidant and antitumor properties. However, the chemical composition of AMC and molecular mechanism of AMC toxicity to HepG2 cells have not yet been elucidated. Hence, this study aimed to investigate the chemical compositions and the underlying mechanisms of the antiproliferative and apoptotic effects of AMC on HepG2. HPLC-MS analysis showed that AMC contain five compounds with chlorogenic acid accounting for 43 percent. Also, AMC strongly inhibited the cell growth and induced apoptosis and cell cycle arrest in HepG2 cells by significantly upregulating the protein expressions of Fas, Fas-L, Bax/Bcl-2, cyto-
c
, cleaved caspase-3, and PARP in a dose-dependent manner, which indicates AMC induces apoptosis in HepG2 cells through both intrinsic and extrinsic pathways. Moreover, AMC provoked the production of ROS, H
2
O
2
, and NO, modulating the PI3K/Akt, MAPK, NFκB and Nrf2 pathways and their downstream transcriptional cascades, ultimately evoked oxidative stress and apoptosis in HpeG2 cells. Further
in vivo
experiments demonstrated that AMC significantly suppressed the tumor growth, suggesting that AMC may be a novel promising agent for hepatocellular carcinoma treatment.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-017-02573-8</identifier><identifier>PMID: 28536473</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>1-Phosphatidylinositol 3-kinase ; 13 ; 13/2 ; 13/31 ; 13/51 ; 14 ; 14/34 ; 631/67/2195 ; 64/60 ; 692/699/67/2195 ; 82 ; 96 ; AKT protein ; Animals ; Antioxidants ; Apoptosis ; Apoptosis - drug effects ; Athyrium ; BAX protein ; Bcl-2 protein ; Caspase ; Caspase-3 ; Cell cycle ; Cell Cycle Checkpoints - drug effects ; Cell Line ; Chinese medicine ; Chlorogenic acid ; Ferns - chemistry ; Hep G2 Cells ; Hepatoblastoma - drug therapy ; Hepatoblastoma - metabolism ; Hepatoblastoma - pathology ; Hepatocellular carcinoma ; Herbal medicine ; High-performance liquid chromatography ; Humanities and Social Sciences ; Humans ; Hydrogen peroxide ; Liquid chromatography ; Liver Neoplasms - drug therapy ; Liver Neoplasms - metabolism ; Liver Neoplasms - pathology ; Male ; MAP kinase ; Mice, Inbred BALB C ; Mice, Nude ; Mitochondria ; Mitochondria - drug effects ; Mitochondria - metabolism ; multidisciplinary ; NF-κB protein ; Oxidative stress ; Oxidative Stress - drug effects ; Plant Extracts - chemistry ; Plant Extracts - pharmacology ; Poly(ADP-ribose) polymerase ; Reactive oxygen species ; Science ; Science (multidisciplinary) ; Toxicity ; Traditional Chinese medicine ; Transcription ; Xenograft Model Antitumor Assays</subject><ispartof>Scientific reports, 2017-05, Vol.7 (1), p.2275-14, Article 2275</ispartof><rights>The Author(s) 2017</rights><rights>Copyright Nature Publishing Group May 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-32d132aadeeebbc2f3f0699f96dc5924d621ea2e1e32b513081df2e7048726c73</citedby><cites>FETCH-LOGICAL-c540t-32d132aadeeebbc2f3f0699f96dc5924d621ea2e1e32b513081df2e7048726c73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1955485520/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1955485520?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28536473$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qi, Guoyuan</creatorcontrib><creatorcontrib>Liu, Zhigang</creatorcontrib><creatorcontrib>Fan, Rong</creatorcontrib><creatorcontrib>Yin, Ziru</creatorcontrib><creatorcontrib>Mi, Yashi</creatorcontrib><creatorcontrib>Ren, Bo</creatorcontrib><creatorcontrib>Liu, Xuebo</creatorcontrib><title>Athyrium multidentatum (Doll.) Ching extract induce apoptosis via mitochondrial dysfunction and oxidative stress in HepG2 cells</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Athyrium multidentatum
(Doll.) Ching (AMC), a unique and nutritious potherb widely distributed in china, has been extensively used in traditional Chinese medicine. Previous studies indicated that AMC extract exhibited antioxidant and antitumor properties. However, the chemical composition of AMC and molecular mechanism of AMC toxicity to HepG2 cells have not yet been elucidated. Hence, this study aimed to investigate the chemical compositions and the underlying mechanisms of the antiproliferative and apoptotic effects of AMC on HepG2. HPLC-MS analysis showed that AMC contain five compounds with chlorogenic acid accounting for 43 percent. Also, AMC strongly inhibited the cell growth and induced apoptosis and cell cycle arrest in HepG2 cells by significantly upregulating the protein expressions of Fas, Fas-L, Bax/Bcl-2, cyto-
c
, cleaved caspase-3, and PARP in a dose-dependent manner, which indicates AMC induces apoptosis in HepG2 cells through both intrinsic and extrinsic pathways. Moreover, AMC provoked the production of ROS, H
2
O
2
, and NO, modulating the PI3K/Akt, MAPK, NFκB and Nrf2 pathways and their downstream transcriptional cascades, ultimately evoked oxidative stress and apoptosis in HpeG2 cells. Further
in vivo
experiments demonstrated that AMC significantly suppressed the tumor growth, suggesting that AMC may be a novel promising agent for hepatocellular carcinoma treatment.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>13</subject><subject>13/2</subject><subject>13/31</subject><subject>13/51</subject><subject>14</subject><subject>14/34</subject><subject>631/67/2195</subject><subject>64/60</subject><subject>692/699/67/2195</subject><subject>82</subject><subject>96</subject><subject>AKT protein</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Athyrium</subject><subject>BAX protein</subject><subject>Bcl-2 protein</subject><subject>Caspase</subject><subject>Caspase-3</subject><subject>Cell cycle</subject><subject>Cell Cycle Checkpoints - drug effects</subject><subject>Cell Line</subject><subject>Chinese medicine</subject><subject>Chlorogenic acid</subject><subject>Ferns - chemistry</subject><subject>Hep G2 Cells</subject><subject>Hepatoblastoma - drug therapy</subject><subject>Hepatoblastoma - metabolism</subject><subject>Hepatoblastoma - pathology</subject><subject>Hepatocellular carcinoma</subject><subject>Herbal medicine</subject><subject>High-performance liquid chromatography</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Hydrogen peroxide</subject><subject>Liquid chromatography</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - pathology</subject><subject>Male</subject><subject>MAP kinase</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Mitochondria</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>multidisciplinary</subject><subject>NF-κB protein</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Plant Extracts - chemistry</subject><subject>Plant Extracts - pharmacology</subject><subject>Poly(ADP-ribose) polymerase</subject><subject>Reactive oxygen species</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Toxicity</subject><subject>Traditional Chinese medicine</subject><subject>Transcription</subject><subject>Xenograft Model Antitumor Assays</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp1kktvEzEUhUcIRKvSP8ACWWJTFlPsa3seG6QqQFupEhtYWx77TuJoZhxsT9Ss-tdxmlKlSHjj1_F3r49OUbxn9JJR3nyOgsm2KSmrSwqy5mXzqjgFKmQJHOD10fqkOI9xTfOQ0ArWvi1OoJG8EjU_LR6u0moX3DyScR6SszglnfLu4qsfhstPZLFy05LgfQraJOImOxskeuM3yUcXydZpMrrkzcpPNjg9ELuL_TyZ5PxE9GSJv3dWJ7dFElPAGDOD3ODmGojBYYjvije9HiKeP81nxa_v334ubsq7H9e3i6u70khBU8nBMg5aW0TsOgM972nVtn1bWSNbELYChhqQIYdOMk4bZnvAmoqmhsrU_Ky4PXCt12u1CW7UYae8durxwIel0iE5M6ASDcuOdj0KpAIM07JvoOs7BCNz5TazvhxYm7kb0ZrsWdDDC-jLm8mt1NJvlRQCaNtkwMUTIPjfM8akRhf3dugJ_RwVaykwWtVCZOnHf6RrP4cpW5VVUopGSqBZBQeVCT7GgP1zM4yqfVzUIS4qx0U9xkXtu_hw_I3nJ3_DkQX8IIj5alpiOKr9f-wfk9fNNg</recordid><startdate>20170523</startdate><enddate>20170523</enddate><creator>Qi, Guoyuan</creator><creator>Liu, Zhigang</creator><creator>Fan, Rong</creator><creator>Yin, Ziru</creator><creator>Mi, Yashi</creator><creator>Ren, Bo</creator><creator>Liu, Xuebo</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><general>Nature Portfolio</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20170523</creationdate><title>Athyrium multidentatum (Doll.) Ching extract induce apoptosis via mitochondrial dysfunction and oxidative stress in HepG2 cells</title><author>Qi, Guoyuan ; Liu, Zhigang ; Fan, Rong ; Yin, Ziru ; Mi, Yashi ; Ren, Bo ; Liu, Xuebo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-32d132aadeeebbc2f3f0699f96dc5924d621ea2e1e32b513081df2e7048726c73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>13</topic><topic>13/2</topic><topic>13/31</topic><topic>13/51</topic><topic>14</topic><topic>14/34</topic><topic>631/67/2195</topic><topic>64/60</topic><topic>692/699/67/2195</topic><topic>82</topic><topic>96</topic><topic>AKT protein</topic><topic>Animals</topic><topic>Antioxidants</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Athyrium</topic><topic>BAX protein</topic><topic>Bcl-2 protein</topic><topic>Caspase</topic><topic>Caspase-3</topic><topic>Cell cycle</topic><topic>Cell Cycle Checkpoints - drug effects</topic><topic>Cell Line</topic><topic>Chinese medicine</topic><topic>Chlorogenic acid</topic><topic>Ferns - chemistry</topic><topic>Hep G2 Cells</topic><topic>Hepatoblastoma - drug therapy</topic><topic>Hepatoblastoma - metabolism</topic><topic>Hepatoblastoma - pathology</topic><topic>Hepatocellular carcinoma</topic><topic>Herbal medicine</topic><topic>High-performance liquid chromatography</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Hydrogen peroxide</topic><topic>Liquid chromatography</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - pathology</topic><topic>Male</topic><topic>MAP kinase</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Mitochondria</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>multidisciplinary</topic><topic>NF-κB protein</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Plant Extracts - chemistry</topic><topic>Plant Extracts - pharmacology</topic><topic>Poly(ADP-ribose) polymerase</topic><topic>Reactive oxygen species</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Toxicity</topic><topic>Traditional Chinese medicine</topic><topic>Transcription</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qi, Guoyuan</creatorcontrib><creatorcontrib>Liu, Zhigang</creatorcontrib><creatorcontrib>Fan, Rong</creatorcontrib><creatorcontrib>Yin, Ziru</creatorcontrib><creatorcontrib>Mi, Yashi</creatorcontrib><creatorcontrib>Ren, Bo</creatorcontrib><creatorcontrib>Liu, Xuebo</creatorcontrib><collection>SpringerOpen</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>ProQuest Biological Science Journals</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qi, Guoyuan</au><au>Liu, Zhigang</au><au>Fan, Rong</au><au>Yin, Ziru</au><au>Mi, Yashi</au><au>Ren, Bo</au><au>Liu, Xuebo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Athyrium multidentatum (Doll.) Ching extract induce apoptosis via mitochondrial dysfunction and oxidative stress in HepG2 cells</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2017-05-23</date><risdate>2017</risdate><volume>7</volume><issue>1</issue><spage>2275</spage><epage>14</epage><pages>2275-14</pages><artnum>2275</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Athyrium multidentatum
(Doll.) Ching (AMC), a unique and nutritious potherb widely distributed in china, has been extensively used in traditional Chinese medicine. Previous studies indicated that AMC extract exhibited antioxidant and antitumor properties. However, the chemical composition of AMC and molecular mechanism of AMC toxicity to HepG2 cells have not yet been elucidated. Hence, this study aimed to investigate the chemical compositions and the underlying mechanisms of the antiproliferative and apoptotic effects of AMC on HepG2. HPLC-MS analysis showed that AMC contain five compounds with chlorogenic acid accounting for 43 percent. Also, AMC strongly inhibited the cell growth and induced apoptosis and cell cycle arrest in HepG2 cells by significantly upregulating the protein expressions of Fas, Fas-L, Bax/Bcl-2, cyto-
c
, cleaved caspase-3, and PARP in a dose-dependent manner, which indicates AMC induces apoptosis in HepG2 cells through both intrinsic and extrinsic pathways. Moreover, AMC provoked the production of ROS, H
2
O
2
, and NO, modulating the PI3K/Akt, MAPK, NFκB and Nrf2 pathways and their downstream transcriptional cascades, ultimately evoked oxidative stress and apoptosis in HpeG2 cells. Further
in vivo
experiments demonstrated that AMC significantly suppressed the tumor growth, suggesting that AMC may be a novel promising agent for hepatocellular carcinoma treatment.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>28536473</pmid><doi>10.1038/s41598-017-02573-8</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| source | PubMed (Medline); Publicly Available Content Database; Full-Text Journals in Chemistry (Open access); Springer Nature - nature.com Journals - Fully Open Access |
| subjects | 1-Phosphatidylinositol 3-kinase 13 13/2 13/31 13/51 14 14/34 631/67/2195 64/60 692/699/67/2195 82 96 AKT protein Animals Antioxidants Apoptosis Apoptosis - drug effects Athyrium BAX protein Bcl-2 protein Caspase Caspase-3 Cell cycle Cell Cycle Checkpoints - drug effects Cell Line Chinese medicine Chlorogenic acid Ferns - chemistry Hep G2 Cells Hepatoblastoma - drug therapy Hepatoblastoma - metabolism Hepatoblastoma - pathology Hepatocellular carcinoma Herbal medicine High-performance liquid chromatography Humanities and Social Sciences Humans Hydrogen peroxide Liquid chromatography Liver Neoplasms - drug therapy Liver Neoplasms - metabolism Liver Neoplasms - pathology Male MAP kinase Mice, Inbred BALB C Mice, Nude Mitochondria Mitochondria - drug effects Mitochondria - metabolism multidisciplinary NF-κB protein Oxidative stress Oxidative Stress - drug effects Plant Extracts - chemistry Plant Extracts - pharmacology Poly(ADP-ribose) polymerase Reactive oxygen species Science Science (multidisciplinary) Toxicity Traditional Chinese medicine Transcription Xenograft Model Antitumor Assays |
| title | Athyrium multidentatum (Doll.) Ching extract induce apoptosis via mitochondrial dysfunction and oxidative stress in HepG2 cells |
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