A potential anti-tumor herbal medicine, Corilagin, inhibits ovarian cancer cell growth through blocking the TGF-[beta] signaling pathways
Background Phyllanthus niruri L. is a well-known hepatoprotective and antiviral medicinal herb. Recently, we identified Corilagin as a major active component with anti-tumor activity in this herbal medicine. Corilagin is a member of the tannin family that has been discovered in many medicinal plants...
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| description | Background Phyllanthus niruri L. is a well-known hepatoprotective and antiviral medicinal herb. Recently, we identified Corilagin as a major active component with anti-tumor activity in this herbal medicine. Corilagin is a member of the tannin family that has been discovered in many medicinal plants and has been used as an anti-inflammatory agent. However, there have been few reports of the anti-tumor effects of Corilagin, and its anti-tumor mechanism has not been investigated clearly. The aim of the present study is to investigate the anticancer properties of Corilagin in ovarian cancer cells. Methods The ovarian cancer cell lines SKOv3ip, Hey and HO-8910PM were treated with Corilagin and analyzed by Sulforhodamine B (SRB) cell proliferation assay, flow cytometry, and reverse phase protein array (RPPA). Corilagin was delivered intraperitoneally to mice bearing SKOv3ip xenografts. Results Corilagin inhibited the growth of the ovarian cancer cell lines SKOv3ip and Hey, with IC50 values of less than 30 [mu]M, while displaying low toxicity against normal ovarian surface epithelium cells, with IC50 values of approximately 160 [mu]M. Corilagin induced cell cycle arrest at the G2/M stage and enhanced apoptosis in ovarian cancer cells. Immunoblotting assays demonstrated that Cyclin B1, Myt1, Phospho-cdc2 and Phospho-Weel were down-regulated after Corilagin treatment. Xenograft tumor growth was significantly lower in the Corilagin-treated group compared with the untreated control group (P |
| doi_str_mv | 10.1186/1472-6882-13-33 |
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Recently, we identified Corilagin as a major active component with anti-tumor activity in this herbal medicine. Corilagin is a member of the tannin family that has been discovered in many medicinal plants and has been used as an anti-inflammatory agent. However, there have been few reports of the anti-tumor effects of Corilagin, and its anti-tumor mechanism has not been investigated clearly. The aim of the present study is to investigate the anticancer properties of Corilagin in ovarian cancer cells. Methods The ovarian cancer cell lines SKOv3ip, Hey and HO-8910PM were treated with Corilagin and analyzed by Sulforhodamine B (SRB) cell proliferation assay, flow cytometry, and reverse phase protein array (RPPA). Corilagin was delivered intraperitoneally to mice bearing SKOv3ip xenografts. Results Corilagin inhibited the growth of the ovarian cancer cell lines SKOv3ip and Hey, with IC50 values of less than 30 [mu]M, while displaying low toxicity against normal ovarian surface epithelium cells, with IC50 values of approximately 160 [mu]M. Corilagin induced cell cycle arrest at the G2/M stage and enhanced apoptosis in ovarian cancer cells. Immunoblotting assays demonstrated that Cyclin B1, Myt1, Phospho-cdc2 and Phospho-Weel were down-regulated after Corilagin treatment. Xenograft tumor growth was significantly lower in the Corilagin-treated group compared with the untreated control group (P <0.05). More interestingly, Corilagin inhibited TGF-[beta] secretion into the culture supernatant of all tested ovarian cancer cell lines and blocked the TGF-[beta]-induced stabilization of Snail. In contrast, a reduction of TGF-[beta] secretion was not observed in cancer cells treated with the cytotoxic drug Paclitaxel, suggesting that Corilagin specifically targets TGF-[beta] secretion. Corilagin blocked the activation of both the canonical Smad and non-canonical ERK/AKT pathways. Conclusions Corilagin extracted from Phyllanthus niruri L. acts as a natural, effective therapeutic agent against the growth of ovarian cancer cells via targeted action against the TGF-[beta]/AKT/ERK/Smad signaling pathways. Keywords: Corilagin, Herbal medicine, TGF-[beta], Ovarian cancer, Epithelial-mesenchymal transition, Cell cycle G2/M arrest, Apoptosis</description><identifier>ISSN: 1472-6882</identifier><identifier>EISSN: 1472-6882</identifier><identifier>DOI: 10.1186/1472-6882-13-33</identifier><language>eng</language><publisher>London: BioMed Central Ltd</publisher><subject>Analysis ; Antimitotic agents ; Antineoplastic agents ; Antiviral agents ; Bone morphogenetic proteins ; Cancer ; Care and treatment ; Chemical properties ; Drug therapy ; Growth ; Health aspects ; Kinases ; Medical research ; Medicinal plants ; Medicine, Botanic ; Medicine, Herbal ; Ovarian cancer ; Paclitaxel ; Phyllanthus ; Proteins ; Science ; Studies ; Tannins ; Transforming growth factors</subject><ispartof>BMC complementary and alternative medicine, 2013-02, Vol.13</ispartof><rights>COPYRIGHT 2013 BioMed Central Ltd.</rights><rights>2013 Jia et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,864,27922,27923</link.rule.ids></links><search><creatorcontrib>Jia, Luoqi</creatorcontrib><creatorcontrib>Jin, Hongyan</creatorcontrib><creatorcontrib>Zhou, Jiayi</creatorcontrib><creatorcontrib>Chen, Lianghua</creatorcontrib><creatorcontrib>Lu, Yiling</creatorcontrib><creatorcontrib>Ming, Yanlin</creatorcontrib><creatorcontrib>Yu, Yinhua</creatorcontrib><title>A potential anti-tumor herbal medicine, Corilagin, inhibits ovarian cancer cell growth through blocking the TGF-[beta] signaling pathways</title><title>BMC complementary and alternative medicine</title><description>Background Phyllanthus niruri L. is a well-known hepatoprotective and antiviral medicinal herb. Recently, we identified Corilagin as a major active component with anti-tumor activity in this herbal medicine. Corilagin is a member of the tannin family that has been discovered in many medicinal plants and has been used as an anti-inflammatory agent. However, there have been few reports of the anti-tumor effects of Corilagin, and its anti-tumor mechanism has not been investigated clearly. The aim of the present study is to investigate the anticancer properties of Corilagin in ovarian cancer cells. Methods The ovarian cancer cell lines SKOv3ip, Hey and HO-8910PM were treated with Corilagin and analyzed by Sulforhodamine B (SRB) cell proliferation assay, flow cytometry, and reverse phase protein array (RPPA). Corilagin was delivered intraperitoneally to mice bearing SKOv3ip xenografts. Results Corilagin inhibited the growth of the ovarian cancer cell lines SKOv3ip and Hey, with IC50 values of less than 30 [mu]M, while displaying low toxicity against normal ovarian surface epithelium cells, with IC50 values of approximately 160 [mu]M. Corilagin induced cell cycle arrest at the G2/M stage and enhanced apoptosis in ovarian cancer cells. Immunoblotting assays demonstrated that Cyclin B1, Myt1, Phospho-cdc2 and Phospho-Weel were down-regulated after Corilagin treatment. Xenograft tumor growth was significantly lower in the Corilagin-treated group compared with the untreated control group (P <0.05). More interestingly, Corilagin inhibited TGF-[beta] secretion into the culture supernatant of all tested ovarian cancer cell lines and blocked the TGF-[beta]-induced stabilization of Snail. In contrast, a reduction of TGF-[beta] secretion was not observed in cancer cells treated with the cytotoxic drug Paclitaxel, suggesting that Corilagin specifically targets TGF-[beta] secretion. Corilagin blocked the activation of both the canonical Smad and non-canonical ERK/AKT pathways. Conclusions Corilagin extracted from Phyllanthus niruri L. acts as a natural, effective therapeutic agent against the growth of ovarian cancer cells via targeted action against the TGF-[beta]/AKT/ERK/Smad signaling pathways. Keywords: Corilagin, Herbal medicine, TGF-[beta], Ovarian cancer, Epithelial-mesenchymal transition, Cell cycle G2/M arrest, Apoptosis</description><subject>Analysis</subject><subject>Antimitotic agents</subject><subject>Antineoplastic agents</subject><subject>Antiviral agents</subject><subject>Bone morphogenetic proteins</subject><subject>Cancer</subject><subject>Care and treatment</subject><subject>Chemical properties</subject><subject>Drug therapy</subject><subject>Growth</subject><subject>Health aspects</subject><subject>Kinases</subject><subject>Medical research</subject><subject>Medicinal plants</subject><subject>Medicine, Botanic</subject><subject>Medicine, Herbal</subject><subject>Ovarian cancer</subject><subject>Paclitaxel</subject><subject>Phyllanthus</subject><subject>Proteins</subject><subject>Science</subject><subject>Studies</subject><subject>Tannins</subject><subject>Transforming growth factors</subject><issn>1472-6882</issn><issn>1472-6882</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNptjs1LxDAQxYso-Hn2GhA82TVp-pEel8VdhQUvehJZpum0jabJmqSKf4L_tV0UXUHm8Ib3fm-YKDpldMKYyC9ZWiRxLkQSMx5zvhMd_Di7W_t-dOj9E6WsECw9iD6mZG0DmqBAExglDkNvHenQVaPTY62kMnhBZtYpDa0yF0SZTlUqeGJfwSkwRIKR6IhErUnr7FvoSOicHdqOVNrKZ2Xa0UByt5jHDxUGeCRetQb0JlhD6N7g3R9Hew1ojyffehTdz6_uZtfx8nZxM5su45YlOY2ZwLxBhhmWNVQJJnWWs6zmBaeCYpMgJo3gIApZZoJWBSDPxsIYVSliWfCj6Ozr7trZlwF9WD3ZwY3P-BXjLOWcspL-Ui1oXCnT2OBA9srL1TTjac6zpNhQk3-ocWrslbQGGzX6fwrnW4UOQYfOWz0EZY3fBj8B63qOXg</recordid><startdate>20130215</startdate><enddate>20130215</enddate><creator>Jia, Luoqi</creator><creator>Jin, Hongyan</creator><creator>Zhou, Jiayi</creator><creator>Chen, Lianghua</creator><creator>Lu, Yiling</creator><creator>Ming, Yanlin</creator><creator>Yu, Yinhua</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>3V.</scope><scope>7TK</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20130215</creationdate><title>A potential anti-tumor herbal medicine, Corilagin, inhibits ovarian cancer cell growth through blocking the TGF-[beta] signaling pathways</title><author>Jia, Luoqi ; Jin, Hongyan ; Zhou, Jiayi ; Chen, Lianghua ; Lu, Yiling ; Ming, Yanlin ; Yu, Yinhua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g1260-18e6fe1e5e9dab2e2d5615d373080ef2ee2f83a87c9580b7ae356fe0efb4ee973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Analysis</topic><topic>Antimitotic agents</topic><topic>Antineoplastic agents</topic><topic>Antiviral agents</topic><topic>Bone morphogenetic proteins</topic><topic>Cancer</topic><topic>Care and treatment</topic><topic>Chemical properties</topic><topic>Drug therapy</topic><topic>Growth</topic><topic>Health aspects</topic><topic>Kinases</topic><topic>Medical research</topic><topic>Medicinal plants</topic><topic>Medicine, Botanic</topic><topic>Medicine, Herbal</topic><topic>Ovarian cancer</topic><topic>Paclitaxel</topic><topic>Phyllanthus</topic><topic>Proteins</topic><topic>Science</topic><topic>Studies</topic><topic>Tannins</topic><topic>Transforming growth factors</topic><toplevel>online_resources</toplevel><creatorcontrib>Jia, Luoqi</creatorcontrib><creatorcontrib>Jin, Hongyan</creatorcontrib><creatorcontrib>Zhou, Jiayi</creatorcontrib><creatorcontrib>Chen, Lianghua</creatorcontrib><creatorcontrib>Lu, Yiling</creatorcontrib><creatorcontrib>Ming, Yanlin</creatorcontrib><creatorcontrib>Yu, Yinhua</creatorcontrib><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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 One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</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 Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</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 China</collection><jtitle>BMC complementary and alternative medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jia, Luoqi</au><au>Jin, Hongyan</au><au>Zhou, Jiayi</au><au>Chen, Lianghua</au><au>Lu, Yiling</au><au>Ming, Yanlin</au><au>Yu, Yinhua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A potential anti-tumor herbal medicine, Corilagin, inhibits ovarian cancer cell growth through blocking the TGF-[beta] signaling pathways</atitle><jtitle>BMC complementary and alternative medicine</jtitle><date>2013-02-15</date><risdate>2013</risdate><volume>13</volume><issn>1472-6882</issn><eissn>1472-6882</eissn><abstract>Background Phyllanthus niruri L. is a well-known hepatoprotective and antiviral medicinal herb. Recently, we identified Corilagin as a major active component with anti-tumor activity in this herbal medicine. Corilagin is a member of the tannin family that has been discovered in many medicinal plants and has been used as an anti-inflammatory agent. However, there have been few reports of the anti-tumor effects of Corilagin, and its anti-tumor mechanism has not been investigated clearly. The aim of the present study is to investigate the anticancer properties of Corilagin in ovarian cancer cells. Methods The ovarian cancer cell lines SKOv3ip, Hey and HO-8910PM were treated with Corilagin and analyzed by Sulforhodamine B (SRB) cell proliferation assay, flow cytometry, and reverse phase protein array (RPPA). Corilagin was delivered intraperitoneally to mice bearing SKOv3ip xenografts. Results Corilagin inhibited the growth of the ovarian cancer cell lines SKOv3ip and Hey, with IC50 values of less than 30 [mu]M, while displaying low toxicity against normal ovarian surface epithelium cells, with IC50 values of approximately 160 [mu]M. Corilagin induced cell cycle arrest at the G2/M stage and enhanced apoptosis in ovarian cancer cells. Immunoblotting assays demonstrated that Cyclin B1, Myt1, Phospho-cdc2 and Phospho-Weel were down-regulated after Corilagin treatment. Xenograft tumor growth was significantly lower in the Corilagin-treated group compared with the untreated control group (P <0.05). More interestingly, Corilagin inhibited TGF-[beta] secretion into the culture supernatant of all tested ovarian cancer cell lines and blocked the TGF-[beta]-induced stabilization of Snail. In contrast, a reduction of TGF-[beta] secretion was not observed in cancer cells treated with the cytotoxic drug Paclitaxel, suggesting that Corilagin specifically targets TGF-[beta] secretion. Corilagin blocked the activation of both the canonical Smad and non-canonical ERK/AKT pathways. Conclusions Corilagin extracted from Phyllanthus niruri L. acts as a natural, effective therapeutic agent against the growth of ovarian cancer cells via targeted action against the TGF-[beta]/AKT/ERK/Smad signaling pathways. Keywords: Corilagin, Herbal medicine, TGF-[beta], Ovarian cancer, Epithelial-mesenchymal transition, Cell cycle G2/M arrest, Apoptosis</abstract><cop>London</cop><pub>BioMed Central Ltd</pub><doi>10.1186/1472-6882-13-33</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Analysis Antimitotic agents Antineoplastic agents Antiviral agents Bone morphogenetic proteins Cancer Care and treatment Chemical properties Drug therapy Growth Health aspects Kinases Medical research Medicinal plants Medicine, Botanic Medicine, Herbal Ovarian cancer Paclitaxel Phyllanthus Proteins Science Studies Tannins Transforming growth factors |
| title | A potential anti-tumor herbal medicine, Corilagin, inhibits ovarian cancer cell growth through blocking the TGF-[beta] signaling pathways |
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