Pterostilbene Suppresses Ovarian Cancer Growth via Induction of Apoptosis and Blockade of Cell Cycle Progression Involving Inhibition of the STAT3 Pathway
A growing body of evidence has demonstrated the promising anti-tumor effects of resveratrol in ovarian cancer cells, including its inhibitory effects on STAT3 activation. Nonetheless, the low bioavailability of resveratrol has reduced its attractiveness as a potential anti-cancer treatment. In contr...
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Veröffentlicht in: | International journal of molecular sciences 2018-07, Vol.19 (7), p.1983 |
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description | A growing body of evidence has demonstrated the promising anti-tumor effects of resveratrol in ovarian cancer cells, including its inhibitory effects on STAT3 activation. Nonetheless, the low bioavailability of resveratrol has reduced its attractiveness as a potential anti-cancer treatment. In contrast, pterostilbene, a stilbenoid and resveratrol analog, has demonstrated superior bioavailability, while possessing significant antitumor activity in multiple solid tumors. In this study, the therapeutic potential of pterostilbene was evaluated in ovarian cancer cells. Pterostilbene reduces cell viability in several different ovarian cancer cell lines by suppressing cell cycle progression and inducing apoptosis. Further molecular study has shown that pterostilbene effectively suppressed phosphorylation of STAT3, as well as STAT3 downstream genes that regulate cell cycle and apoptosis, indicating that inhibition of STAT3 pathway may be involved in its anti-tumor activity. The addition of pterostilbene to the commonly used chemotherapy cisplatin demonstrated synergistic antiproliferative activity in several ovarian cancer cell lines. Pterostilbene additionally inhibited cell migration in multiple ovarian cancer cell lines. The above results suggest that pterostilbene facilitates significant anti-tumor activity in ovarian cancer via anti-proliferative and pro-apoptotic mechanisms, possibly via downregulation of JAK/STAT3 pathway. Pterostilbene thus presents as an attractive non-toxic alternative for potential adjuvant or maintenance chemotherapy in ovarian cancer. |
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Nonetheless, the low bioavailability of resveratrol has reduced its attractiveness as a potential anti-cancer treatment. In contrast, pterostilbene, a stilbenoid and resveratrol analog, has demonstrated superior bioavailability, while possessing significant antitumor activity in multiple solid tumors. In this study, the therapeutic potential of pterostilbene was evaluated in ovarian cancer cells. Pterostilbene reduces cell viability in several different ovarian cancer cell lines by suppressing cell cycle progression and inducing apoptosis. Further molecular study has shown that pterostilbene effectively suppressed phosphorylation of STAT3, as well as STAT3 downstream genes that regulate cell cycle and apoptosis, indicating that inhibition of STAT3 pathway may be involved in its anti-tumor activity. The addition of pterostilbene to the commonly used chemotherapy cisplatin demonstrated synergistic antiproliferative activity in several ovarian cancer cell lines. Pterostilbene additionally inhibited cell migration in multiple ovarian cancer cell lines. The above results suggest that pterostilbene facilitates significant anti-tumor activity in ovarian cancer via anti-proliferative and pro-apoptotic mechanisms, possibly via downregulation of JAK/STAT3 pathway. Pterostilbene thus presents as an attractive non-toxic alternative for potential adjuvant or maintenance chemotherapy in ovarian cancer.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms19071983</identifier><identifier>PMID: 29986501</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Antitumor activity ; Apoptosis ; Bioavailability ; Cell cycle ; Chemotherapy ; Cisplatin ; Ovarian cancer ; Phosphorylation ; Resveratrol ; Solid tumors ; Stat3 protein ; Tumor cell lines ; Tumors</subject><ispartof>International journal of molecular sciences, 2018-07, Vol.19 (7), p.1983</ispartof><rights>2018. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 by the authors. 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-c587348ef9881f256509f71a8c41329004fcd35abc01be11f1d890da3caa364d3</citedby><cites>FETCH-LOGICAL-c478t-c587348ef9881f256509f71a8c41329004fcd35abc01be11f1d890da3caa364d3</cites><orcidid>0000-0003-1314-2190</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/PMC6073736/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073736/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29986501$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wen, Wei</creatorcontrib><creatorcontrib>Lowe, Gina</creatorcontrib><creatorcontrib>Roberts, Cai M</creatorcontrib><creatorcontrib>Finlay, James</creatorcontrib><creatorcontrib>Han, Ernest S</creatorcontrib><creatorcontrib>Glackin, Carlotta A</creatorcontrib><creatorcontrib>Dellinger, Thanh Hue</creatorcontrib><title>Pterostilbene Suppresses Ovarian Cancer Growth via Induction of Apoptosis and Blockade of Cell Cycle Progression Involving Inhibition of the STAT3 Pathway</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>A growing body of evidence has demonstrated the promising anti-tumor effects of resveratrol in ovarian cancer cells, including its inhibitory effects on STAT3 activation. 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Pterostilbene additionally inhibited cell migration in multiple ovarian cancer cell lines. The above results suggest that pterostilbene facilitates significant anti-tumor activity in ovarian cancer via anti-proliferative and pro-apoptotic mechanisms, possibly via downregulation of JAK/STAT3 pathway. Pterostilbene thus presents as an attractive non-toxic alternative for potential adjuvant or maintenance chemotherapy in ovarian cancer.</description><subject>Antitumor activity</subject><subject>Apoptosis</subject><subject>Bioavailability</subject><subject>Cell cycle</subject><subject>Chemotherapy</subject><subject>Cisplatin</subject><subject>Ovarian cancer</subject><subject>Phosphorylation</subject><subject>Resveratrol</subject><subject>Solid tumors</subject><subject>Stat3 protein</subject><subject>Tumor cell lines</subject><subject>Tumors</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkUuP0zAURiMEYh6wY40ssWFBwY887A1SJ4Kh0khTibK2bhyncUntYDsZ9a_wa8fVPFRY-Ur3-LM_nSx7R_BnxgT-Ynb7QASuiODsRXZOckoXGJfVy5P5LLsIYYcxZbQQr7MzKgQvC0zOs7_rqL0L0QyNthr9nMbR6xB0QLczeAMW1WCV9ujau7vYo9kAWtl2UtE4i1yHlqMbowsmILAtuhqc-g2tPm5qPQyoPqhBo7V322Ps8c7Kzm6Yjd2mqTeNeQqKfXp-s9wwtIbY38HhTfaqgyHot4_nZfbr-7dN_WNxc3u9qpc3C5VXPC5UwSuWc90JzklHi9RLdBUBrnLCqMA471TLCmgUJo0mpCMtF7gFpgBYmbfsMvv6kDtOzV63StvoYZCjN3vwB-nAyH831vRy62ZZ4opVrEwBHx8DvPsz6RDl3gSV2oPVbgqSJgNc0ILjhH74D925ydtUT1KCRS4YI3miPj1QKqkJXnfPnyFYHqXLU-kJf39a4Bl-sszuAaexqsw</recordid><startdate>20180707</startdate><enddate>20180707</enddate><creator>Wen, Wei</creator><creator>Lowe, Gina</creator><creator>Roberts, Cai M</creator><creator>Finlay, James</creator><creator>Han, Ernest S</creator><creator>Glackin, Carlotta A</creator><creator>Dellinger, Thanh Hue</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1314-2190</orcidid></search><sort><creationdate>20180707</creationdate><title>Pterostilbene Suppresses Ovarian Cancer Growth via Induction of Apoptosis and Blockade of Cell Cycle Progression Involving Inhibition of the STAT3 Pathway</title><author>Wen, Wei ; 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subjects | Antitumor activity Apoptosis Bioavailability Cell cycle Chemotherapy Cisplatin Ovarian cancer Phosphorylation Resveratrol Solid tumors Stat3 protein Tumor cell lines Tumors |
title | Pterostilbene Suppresses Ovarian Cancer Growth via Induction of Apoptosis and Blockade of Cell Cycle Progression Involving Inhibition of the STAT3 Pathway |
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