Resveratrol induces cell death through ROS‑dependent downregulation of Notch1/PTEN/Akt signaling in ovarian cancer cells
Resveratrol, a natural polyphenol compound, has been reported to exert anticancer activity in various cancer cells. The present study investigated the effect and underlying mechanisms of resveratrol in the human ovarian cancer cell lines, A2780 and SKOV3. Treatment with resveratrol induced apoptotic...
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| Veröffentlicht in: | Molecular medicine reports 2019-04, Vol.19 (4), p.3353-3360 |
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| description | Resveratrol, a natural polyphenol compound, has been reported to exert anticancer activity in various cancer cells. The present study investigated the effect and underlying mechanisms of resveratrol in the human ovarian cancer cell lines, A2780 and SKOV3. Treatment with resveratrol induced apoptotic cell death in dose‑ and time‑dependent manners, as well as a transient increase of reactive oxygen species (ROS) generation. Resveratrol‑induced cell death was attenuated by the antioxidant, N‑acetylcysteine (NAC), suggesting that ROS were involved in the observed cell death. Treatment with resveratrol resulted in a ROS‑dependent decrease of Notch1 signaling. When cells were transfected to overexpress Notch1 using EF.hlCN1.CMV.GFP, resveratrol‑induced cell death was blocked. Western blot analysis demonstrated that resveratrol also upregulated phospho‑phosphatase and tensin homolog (p‑PTEN) and downregulated phospho‑Akt (p‑Akt). Overexpression of p‑Akt by transfection with a constitutively active form (caAkt), and the p‑PTEN inhibitor SF1670 prevented resveratrol‑induced cell death. The caspase‑3 inhibitor z‑DEVD‑FMK significantly attenuated the resveratrol‑induced caspase‑3 cleavage. Taken together, the results of the present study suggest that resveratrol induces caspase‑dependent cell death through suppression of Notch1 and PTEN/Akt signaling and it is mediated by increased ROS generation in human ovarian cancer cells. |
| doi_str_mv | 10.3892/mmr.2019.9962 |
| format | Article |
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The present study investigated the effect and underlying mechanisms of resveratrol in the human ovarian cancer cell lines, A2780 and SKOV3. Treatment with resveratrol induced apoptotic cell death in dose‑ and time‑dependent manners, as well as a transient increase of reactive oxygen species (ROS) generation. Resveratrol‑induced cell death was attenuated by the antioxidant, N‑acetylcysteine (NAC), suggesting that ROS were involved in the observed cell death. Treatment with resveratrol resulted in a ROS‑dependent decrease of Notch1 signaling. When cells were transfected to overexpress Notch1 using EF.hlCN1.CMV.GFP, resveratrol‑induced cell death was blocked. Western blot analysis demonstrated that resveratrol also upregulated phospho‑phosphatase and tensin homolog (p‑PTEN) and downregulated phospho‑Akt (p‑Akt). Overexpression of p‑Akt by transfection with a constitutively active form (caAkt), and the p‑PTEN inhibitor SF1670 prevented resveratrol‑induced cell death. The caspase‑3 inhibitor z‑DEVD‑FMK significantly attenuated the resveratrol‑induced caspase‑3 cleavage. Taken together, the results of the present study suggest that resveratrol induces caspase‑dependent cell death through suppression of Notch1 and PTEN/Akt signaling and it is mediated by increased ROS generation in human ovarian cancer cells.</description><identifier>ISSN: 1791-2997</identifier><identifier>EISSN: 1791-3004</identifier><identifier>DOI: 10.3892/mmr.2019.9962</identifier><identifier>PMID: 30816513</identifier><language>eng</language><publisher>Greece: Spandidos Publications</publisher><subject>Acetylcysteine ; AKT protein ; Antioxidants ; Antioxidants (Nutrients) ; Antitumor activity ; Apoptosis ; Biochemistry ; Cancer cells ; Cancer therapies ; Cancer treatment ; Caspase ; Caspase-3 ; Cell death ; Cellular signal transduction ; Cytochrome ; Drug resistance ; EDTA ; Immunoglobulins ; Membranes ; Notch1 protein ; Ovarian cancer ; Phosphatases ; PTEN protein ; Reactive oxygen species ; Resveratrol ; Software ; Tensin ; Transfection ; Tumor cell lines</subject><ispartof>Molecular medicine reports, 2019-04, Vol.19 (4), p.3353-3360</ispartof><rights>COPYRIGHT 2019 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2019</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c427t-cf082a70e1d460c85f1ddbcb230b4ca1fc9d76fe87ffd7f8374cb912212ef2dd3</citedby><cites>FETCH-LOGICAL-c427t-cf082a70e1d460c85f1ddbcb230b4ca1fc9d76fe87ffd7f8374cb912212ef2dd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30816513$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Thae Hyun</creatorcontrib><creatorcontrib>Park, Ji Hye</creatorcontrib><creatorcontrib>Woo, Jae Suk</creatorcontrib><title>Resveratrol induces cell death through ROS‑dependent downregulation of Notch1/PTEN/Akt signaling in ovarian cancer cells</title><title>Molecular medicine reports</title><addtitle>Mol Med Rep</addtitle><description>Resveratrol, a natural polyphenol compound, has been reported to exert anticancer activity in various cancer cells. The present study investigated the effect and underlying mechanisms of resveratrol in the human ovarian cancer cell lines, A2780 and SKOV3. Treatment with resveratrol induced apoptotic cell death in dose‑ and time‑dependent manners, as well as a transient increase of reactive oxygen species (ROS) generation. Resveratrol‑induced cell death was attenuated by the antioxidant, N‑acetylcysteine (NAC), suggesting that ROS were involved in the observed cell death. Treatment with resveratrol resulted in a ROS‑dependent decrease of Notch1 signaling. When cells were transfected to overexpress Notch1 using EF.hlCN1.CMV.GFP, resveratrol‑induced cell death was blocked. Western blot analysis demonstrated that resveratrol also upregulated phospho‑phosphatase and tensin homolog (p‑PTEN) and downregulated phospho‑Akt (p‑Akt). Overexpression of p‑Akt by transfection with a constitutively active form (caAkt), and the p‑PTEN inhibitor SF1670 prevented resveratrol‑induced cell death. The caspase‑3 inhibitor z‑DEVD‑FMK significantly attenuated the resveratrol‑induced caspase‑3 cleavage. Taken together, the results of the present study suggest that resveratrol induces caspase‑dependent cell death through suppression of Notch1 and PTEN/Akt signaling and it is mediated by increased ROS generation in human ovarian cancer cells.</description><subject>Acetylcysteine</subject><subject>AKT protein</subject><subject>Antioxidants</subject><subject>Antioxidants (Nutrients)</subject><subject>Antitumor activity</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Cancer cells</subject><subject>Cancer therapies</subject><subject>Cancer treatment</subject><subject>Caspase</subject><subject>Caspase-3</subject><subject>Cell death</subject><subject>Cellular signal transduction</subject><subject>Cytochrome</subject><subject>Drug resistance</subject><subject>EDTA</subject><subject>Immunoglobulins</subject><subject>Membranes</subject><subject>Notch1 protein</subject><subject>Ovarian cancer</subject><subject>Phosphatases</subject><subject>PTEN protein</subject><subject>Reactive oxygen species</subject><subject>Resveratrol</subject><subject>Software</subject><subject>Tensin</subject><subject>Transfection</subject><subject>Tumor cell lines</subject><issn>1791-2997</issn><issn>1791-3004</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNptkU1v1DAQhiMEoqVw5IosceGyux47Xz6uqvIhVS0q5Ww59jjrktiL7RTBib_AX-SXkNAFBEI-jGU983pGT1E8BbrmrWCbcYxrRkGshajZveIYGgErTml5_3BnQjRHxaOUbiitK1aJh8URpy3UFfDj4ssVpluMKscwEOfNpDERjcNADKq8I3kXw9TvyNXlu-9fvxncozfoMzHhk4_YT4PKLngSLLkIWe9g8_b67GKz_ZBJcr1Xg_P9HEvCrYpOeaKV1xh_fpAeFw-sGhI-OdST4v3Ls-vT16vzy1dvTrfnK12yJq-0pS1TDUUwZU11W1kwptMd47QrtQKrhWlqi21jrWlsy5tSdwIYA4aWGcNPihd3ufsYPk6YshxdWiZQHsOUJIO2oayEsp7R5_-gN2GK8xoLJXglSiHgD9WrAaXzNuSo9BIqt1ULHIAKOlPr_1DzMTg6HTxaN7__1bC6a9AxpBTRyn10o4qfJVC5uJaza7m4lovrmX92GHbqRjS_6V9y-Q_0qaW7</recordid><startdate>20190401</startdate><enddate>20190401</enddate><creator>Kim, Thae Hyun</creator><creator>Park, Ji Hye</creator><creator>Woo, Jae Suk</creator><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</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>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20190401</creationdate><title>Resveratrol induces cell death through ROS‑dependent downregulation of Notch1/PTEN/Akt signaling in ovarian cancer cells</title><author>Kim, Thae Hyun ; Park, Ji Hye ; Woo, Jae Suk</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c427t-cf082a70e1d460c85f1ddbcb230b4ca1fc9d76fe87ffd7f8374cb912212ef2dd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Acetylcysteine</topic><topic>AKT protein</topic><topic>Antioxidants</topic><topic>Antioxidants (Nutrients)</topic><topic>Antitumor activity</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Cancer cells</topic><topic>Cancer therapies</topic><topic>Cancer treatment</topic><topic>Caspase</topic><topic>Caspase-3</topic><topic>Cell death</topic><topic>Cellular signal transduction</topic><topic>Cytochrome</topic><topic>Drug resistance</topic><topic>EDTA</topic><topic>Immunoglobulins</topic><topic>Membranes</topic><topic>Notch1 protein</topic><topic>Ovarian cancer</topic><topic>Phosphatases</topic><topic>PTEN protein</topic><topic>Reactive oxygen species</topic><topic>Resveratrol</topic><topic>Software</topic><topic>Tensin</topic><topic>Transfection</topic><topic>Tumor cell lines</topic><toplevel>online_resources</toplevel><creatorcontrib>Kim, Thae Hyun</creatorcontrib><creatorcontrib>Park, Ji Hye</creatorcontrib><creatorcontrib>Woo, Jae Suk</creatorcontrib><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>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</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>Biological Science 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 China</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular medicine reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Thae Hyun</au><au>Park, Ji Hye</au><au>Woo, Jae Suk</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Resveratrol induces cell death through ROS‑dependent downregulation of Notch1/PTEN/Akt signaling in ovarian cancer cells</atitle><jtitle>Molecular medicine reports</jtitle><addtitle>Mol Med Rep</addtitle><date>2019-04-01</date><risdate>2019</risdate><volume>19</volume><issue>4</issue><spage>3353</spage><epage>3360</epage><pages>3353-3360</pages><issn>1791-2997</issn><eissn>1791-3004</eissn><abstract>Resveratrol, a natural polyphenol compound, has been reported to exert anticancer activity in various cancer cells. The present study investigated the effect and underlying mechanisms of resveratrol in the human ovarian cancer cell lines, A2780 and SKOV3. Treatment with resveratrol induced apoptotic cell death in dose‑ and time‑dependent manners, as well as a transient increase of reactive oxygen species (ROS) generation. Resveratrol‑induced cell death was attenuated by the antioxidant, N‑acetylcysteine (NAC), suggesting that ROS were involved in the observed cell death. Treatment with resveratrol resulted in a ROS‑dependent decrease of Notch1 signaling. When cells were transfected to overexpress Notch1 using EF.hlCN1.CMV.GFP, resveratrol‑induced cell death was blocked. Western blot analysis demonstrated that resveratrol also upregulated phospho‑phosphatase and tensin homolog (p‑PTEN) and downregulated phospho‑Akt (p‑Akt). Overexpression of p‑Akt by transfection with a constitutively active form (caAkt), and the p‑PTEN inhibitor SF1670 prevented resveratrol‑induced cell death. The caspase‑3 inhibitor z‑DEVD‑FMK significantly attenuated the resveratrol‑induced caspase‑3 cleavage. Taken together, the results of the present study suggest that resveratrol induces caspase‑dependent cell death through suppression of Notch1 and PTEN/Akt signaling and it is mediated by increased ROS generation in human ovarian cancer cells.</abstract><cop>Greece</cop><pub>Spandidos Publications</pub><pmid>30816513</pmid><doi>10.3892/mmr.2019.9962</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Molecular medicine reports, 2019-04, Vol.19 (4), p.3353-3360 |
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| source | Spandidos Publications Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Acetylcysteine AKT protein Antioxidants Antioxidants (Nutrients) Antitumor activity Apoptosis Biochemistry Cancer cells Cancer therapies Cancer treatment Caspase Caspase-3 Cell death Cellular signal transduction Cytochrome Drug resistance EDTA Immunoglobulins Membranes Notch1 protein Ovarian cancer Phosphatases PTEN protein Reactive oxygen species Resveratrol Software Tensin Transfection Tumor cell lines |
| title | Resveratrol induces cell death through ROS‑dependent downregulation of Notch1/PTEN/Akt signaling in ovarian cancer cells |
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