In vivo and in vitro suppression of hepatocellular carcinoma by EF24, a curcumin analog
The synthetic compound 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) is a potent analog of curcumin that exhibits enhanced biological activity and bioavailability without increasing toxicity. EF24 exerts antitumor activity by arresting the cell cycle and inducing apoptosis, suppressing many type...
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| Veröffentlicht in: | PloS one 2012-10, Vol.7 (10), p.e48075-e48075 |
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| creator | Liu, Haitao Liang, Yingjian Wang, Luoluo Tian, Lantian Song, Ruipeng Han, Tianwen Pan, Shangha Liu, Lianxin |
| description | The synthetic compound 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) is a potent analog of curcumin that exhibits enhanced biological activity and bioavailability without increasing toxicity. EF24 exerts antitumor activity by arresting the cell cycle and inducing apoptosis, suppressing many types of cancer cells in vitro. The antiproliferative and antiangiogenic properties of EF24 provide theoretical support for its development and application to liver cancers. We investigated the in vitro and in vivo activities of EF24 on liver cancer to better understand its therapeutic effects and mechanisms. EF24 induced significant apoptosis and G2/M-phase cell cycle arrest in mouse liver cancer cell lines, Hepa1-6 and H22. The expression levels of G2/M cell cycle regulating factors, cyclin B1 and Cdc2, were significantly decreased, pp53, p53, and p21 were significantly increased in EF24-treated cells. In addition, EF24 treatment significantly reduced Bcl-2 concomitant with an increase in Bax, enhanced the release of cytochrome c from the mitochondria into the cytosol, resulting in an upregulation of cleaved-caspase-3, which promoted poly (ADP-ribose) polymerase cleavage. EF24-treated cells also displayed decreases in phosphorylated Akt, phosphorylated extracellular signal-regulated kinase and vascular endothelial growth factor. Our in vitro protein expression data were confirmed in vivo using a subcutaneous hepatocellular carcinoma (HCC) tumor model. This mouse HCC model confirmed that total body weight was unchanged following EF24 treatment, although tumor weight was significantly decreased. Using an orthotopic HCC model, EF24 significantly reduced the liver/body weight ratio and relative tumor areas compared to the control group. In situ detection of apoptotic cells and quantification of Ki-67, a biomarker of cell proliferation, all indicated significant tumor suppression with EF24 treatment. These results suggest that EF24 exhibits anti-tumor activity on liver cancer cells via mitochondria-dependent apoptosis and inducing cell cycle arrest coupled with antiangiogenesis. The demonstrated activities of EF24 support its further evaluation as a treatment for human liver cancers. |
| doi_str_mv | 10.1371/journal.pone.0048075 |
| format | Article |
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EF24 exerts antitumor activity by arresting the cell cycle and inducing apoptosis, suppressing many types of cancer cells in vitro. The antiproliferative and antiangiogenic properties of EF24 provide theoretical support for its development and application to liver cancers. We investigated the in vitro and in vivo activities of EF24 on liver cancer to better understand its therapeutic effects and mechanisms. EF24 induced significant apoptosis and G2/M-phase cell cycle arrest in mouse liver cancer cell lines, Hepa1-6 and H22. The expression levels of G2/M cell cycle regulating factors, cyclin B1 and Cdc2, were significantly decreased, pp53, p53, and p21 were significantly increased in EF24-treated cells. In addition, EF24 treatment significantly reduced Bcl-2 concomitant with an increase in Bax, enhanced the release of cytochrome c from the mitochondria into the cytosol, resulting in an upregulation of cleaved-caspase-3, which promoted poly (ADP-ribose) polymerase cleavage. EF24-treated cells also displayed decreases in phosphorylated Akt, phosphorylated extracellular signal-regulated kinase and vascular endothelial growth factor. Our in vitro protein expression data were confirmed in vivo using a subcutaneous hepatocellular carcinoma (HCC) tumor model. This mouse HCC model confirmed that total body weight was unchanged following EF24 treatment, although tumor weight was significantly decreased. Using an orthotopic HCC model, EF24 significantly reduced the liver/body weight ratio and relative tumor areas compared to the control group. In situ detection of apoptotic cells and quantification of Ki-67, a biomarker of cell proliferation, all indicated significant tumor suppression with EF24 treatment. These results suggest that EF24 exhibits anti-tumor activity on liver cancer cells via mitochondria-dependent apoptosis and inducing cell cycle arrest coupled with antiangiogenesis. The demonstrated activities of EF24 support its further evaluation as a treatment for human liver cancers.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0048075</identifier><identifier>PMID: 23118928</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenosine diphosphate ; AKT protein ; Angiogenesis Inhibitors - pharmacology ; Animals ; Antiangiogenics ; Anticancer properties ; Antitumor activity ; Antitumor agents ; Apoptosis ; Apoptosis - drug effects ; Bax protein ; Bcl-2 protein ; Benzylidene Compounds - pharmacology ; Bioavailability ; Biocompatibility ; Biological activity ; Biology ; Biomarkers ; Body weight ; Cancer ; Carcinoma, Hepatocellular - blood supply ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - pathology ; Caspase ; Caspase-3 ; Cdc2 protein ; Cell cycle ; Cell Cycle Checkpoints - drug effects ; Cell growth ; Cell Line, Tumor ; Cell proliferation ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Curcumin ; Cyclin B1 ; Cytochrome ; Cytochrome c ; Cytosol ; Data processing ; Extracellular signal-regulated kinase ; Health aspects ; Hepatocellular carcinoma ; Hepatocytes ; Humans ; In vivo methods and tests ; Kinases ; Liver ; Liver cancer ; Liver Neoplasms, Experimental - blood supply ; Liver Neoplasms, Experimental - drug therapy ; Liver Neoplasms, Experimental - pathology ; Male ; MAP Kinase Signaling System - drug effects ; Medicine ; Mice ; Mice, Inbred C57BL ; Mitochondria ; Piperidones - pharmacology ; Ribose ; Rodents ; Toxicity ; Tumor Burden - drug effects ; Tumor cell lines ; Tumor proteins ; Tumor suppression ; Ubiquitin-Protein Ligases - drug effects ; Ubiquitin-Protein Ligases - physiology ; Vascular endothelial growth factor ; Weight reduction ; Xenograft Model Antitumor Assays</subject><ispartof>PloS one, 2012-10, Vol.7 (10), p.e48075-e48075</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Liu et al 2012 Liu et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-cc3a4ece92f0b4c8b065c09b02b4ca823382604f56e656a63bc15925ce5c85d43</citedby><cites>FETCH-LOGICAL-c758t-cc3a4ece92f0b4c8b065c09b02b4ca823382604f56e656a63bc15925ce5c85d43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485291/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485291/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79472,79473</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23118928$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>El-Rifai, Wael</contributor><creatorcontrib>Liu, Haitao</creatorcontrib><creatorcontrib>Liang, Yingjian</creatorcontrib><creatorcontrib>Wang, Luoluo</creatorcontrib><creatorcontrib>Tian, Lantian</creatorcontrib><creatorcontrib>Song, Ruipeng</creatorcontrib><creatorcontrib>Han, Tianwen</creatorcontrib><creatorcontrib>Pan, Shangha</creatorcontrib><creatorcontrib>Liu, Lianxin</creatorcontrib><title>In vivo and in vitro suppression of hepatocellular carcinoma by EF24, a curcumin analog</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The synthetic compound 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) is a potent analog of curcumin that exhibits enhanced biological activity and bioavailability without increasing toxicity. EF24 exerts antitumor activity by arresting the cell cycle and inducing apoptosis, suppressing many types of cancer cells in vitro. The antiproliferative and antiangiogenic properties of EF24 provide theoretical support for its development and application to liver cancers. We investigated the in vitro and in vivo activities of EF24 on liver cancer to better understand its therapeutic effects and mechanisms. EF24 induced significant apoptosis and G2/M-phase cell cycle arrest in mouse liver cancer cell lines, Hepa1-6 and H22. The expression levels of G2/M cell cycle regulating factors, cyclin B1 and Cdc2, were significantly decreased, pp53, p53, and p21 were significantly increased in EF24-treated cells. In addition, EF24 treatment significantly reduced Bcl-2 concomitant with an increase in Bax, enhanced the release of cytochrome c from the mitochondria into the cytosol, resulting in an upregulation of cleaved-caspase-3, which promoted poly (ADP-ribose) polymerase cleavage. EF24-treated cells also displayed decreases in phosphorylated Akt, phosphorylated extracellular signal-regulated kinase and vascular endothelial growth factor. Our in vitro protein expression data were confirmed in vivo using a subcutaneous hepatocellular carcinoma (HCC) tumor model. This mouse HCC model confirmed that total body weight was unchanged following EF24 treatment, although tumor weight was significantly decreased. Using an orthotopic HCC model, EF24 significantly reduced the liver/body weight ratio and relative tumor areas compared to the control group. In situ detection of apoptotic cells and quantification of Ki-67, a biomarker of cell proliferation, all indicated significant tumor suppression with EF24 treatment. These results suggest that EF24 exhibits anti-tumor activity on liver cancer cells via mitochondria-dependent apoptosis and inducing cell cycle arrest coupled with antiangiogenesis. The demonstrated activities of EF24 support its further evaluation as a treatment for human liver cancers.</description><subject>Adenosine diphosphate</subject><subject>AKT protein</subject><subject>Angiogenesis Inhibitors - pharmacology</subject><subject>Animals</subject><subject>Antiangiogenics</subject><subject>Anticancer properties</subject><subject>Antitumor activity</subject><subject>Antitumor agents</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Bax protein</subject><subject>Bcl-2 protein</subject><subject>Benzylidene Compounds - pharmacology</subject><subject>Bioavailability</subject><subject>Biocompatibility</subject><subject>Biological activity</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Body weight</subject><subject>Cancer</subject><subject>Carcinoma, Hepatocellular - blood supply</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Caspase</subject><subject>Caspase-3</subject><subject>Cdc2 protein</subject><subject>Cell cycle</subject><subject>Cell Cycle Checkpoints - drug effects</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Curcumin</subject><subject>Cyclin B1</subject><subject>Cytochrome</subject><subject>Cytochrome c</subject><subject>Cytosol</subject><subject>Data processing</subject><subject>Extracellular signal-regulated kinase</subject><subject>Health aspects</subject><subject>Hepatocellular carcinoma</subject><subject>Hepatocytes</subject><subject>Humans</subject><subject>In vivo methods and tests</subject><subject>Kinases</subject><subject>Liver</subject><subject>Liver cancer</subject><subject>Liver Neoplasms, Experimental - blood supply</subject><subject>Liver Neoplasms, Experimental - drug therapy</subject><subject>Liver Neoplasms, Experimental - pathology</subject><subject>Male</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mitochondria</subject><subject>Piperidones - pharmacology</subject><subject>Ribose</subject><subject>Rodents</subject><subject>Toxicity</subject><subject>Tumor Burden - drug effects</subject><subject>Tumor cell lines</subject><subject>Tumor proteins</subject><subject>Tumor suppression</subject><subject>Ubiquitin-Protein Ligases - drug effects</subject><subject>Ubiquitin-Protein Ligases - physiology</subject><subject>Vascular endothelial growth factor</subject><subject>Weight reduction</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkktr3DAUhU1padK0_6C0hkJpoTPV2_KmEELSDgQCfS6FLF_PaLAtR7KH5N9H7jhhXLIoXuj13XOl45MkrzFaYprhz1s3-FbXy861sESISZTxJ8kxzilZCILo04P5UfIihC1CnEohnidHhGIscyKPkz-rNt3ZnUt1W6Z2nPfepWHoOg8hWNemrko30OneGajrodY-Ndob27pGp8Vten5B2KdUp2bwZmiigo6XcuuXybNK1wFeTeNJ8uvi_OfZt8Xl1dfV2enlwmRc9gtjqGZgICcVKpiRBRLcoLxAJK60JJRKIhCruADBhRa0MJjnhBvgRvKS0ZPk7V63q11QkydBYUoiTxjJIrHaE6XTW9V522h_q5y26u-G82ulfW9NDQoB4UVWAgKWMQIozzOqSwk5F1JEi6PWl6nbUDRQGmh7r-uZ6PyktRu1djtFmeQkx1HgwyTg3fUAoVeNDaOxugU3xHtjIgTOOEMRffcP-vjrJmqt4wNsW7nY14yi6pRlIpciQ2Pb5SNU_EporIkBqmzcnxV8nBVEpoebfq2HENTqx_f_Z69-z9n3B-wGdN1vgquHPiYtzEG2B413IXioHkzGSI35v3dDjflXU_5j2ZvDH_RQdB94egciVv4x</recordid><startdate>20121031</startdate><enddate>20121031</enddate><creator>Liu, Haitao</creator><creator>Liang, Yingjian</creator><creator>Wang, Luoluo</creator><creator>Tian, Lantian</creator><creator>Song, Ruipeng</creator><creator>Han, Tianwen</creator><creator>Pan, Shangha</creator><creator>Liu, Lianxin</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20121031</creationdate><title>In vivo and in vitro suppression of hepatocellular carcinoma by EF24, a curcumin analog</title><author>Liu, Haitao ; Liang, Yingjian ; Wang, Luoluo ; Tian, Lantian ; Song, Ruipeng ; Han, Tianwen ; Pan, Shangha ; Liu, Lianxin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-cc3a4ece92f0b4c8b065c09b02b4ca823382604f56e656a63bc15925ce5c85d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adenosine diphosphate</topic><topic>AKT protein</topic><topic>Angiogenesis Inhibitors - 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drug effects</topic><topic>Curcumin</topic><topic>Cyclin B1</topic><topic>Cytochrome</topic><topic>Cytochrome c</topic><topic>Cytosol</topic><topic>Data processing</topic><topic>Extracellular signal-regulated kinase</topic><topic>Health aspects</topic><topic>Hepatocellular carcinoma</topic><topic>Hepatocytes</topic><topic>Humans</topic><topic>In vivo methods and tests</topic><topic>Kinases</topic><topic>Liver</topic><topic>Liver cancer</topic><topic>Liver Neoplasms, Experimental - blood supply</topic><topic>Liver Neoplasms, Experimental - drug therapy</topic><topic>Liver Neoplasms, Experimental - pathology</topic><topic>Male</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Medicine</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mitochondria</topic><topic>Piperidones - pharmacology</topic><topic>Ribose</topic><topic>Rodents</topic><topic>Toxicity</topic><topic>Tumor Burden - drug effects</topic><topic>Tumor cell lines</topic><topic>Tumor proteins</topic><topic>Tumor suppression</topic><topic>Ubiquitin-Protein Ligases - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</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><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Haitao</au><au>Liang, Yingjian</au><au>Wang, Luoluo</au><au>Tian, Lantian</au><au>Song, Ruipeng</au><au>Han, Tianwen</au><au>Pan, Shangha</au><au>Liu, Lianxin</au><au>El-Rifai, Wael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vivo and in vitro suppression of hepatocellular carcinoma by EF24, a curcumin analog</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-10-31</date><risdate>2012</risdate><volume>7</volume><issue>10</issue><spage>e48075</spage><epage>e48075</epage><pages>e48075-e48075</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The synthetic compound 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) is a potent analog of curcumin that exhibits enhanced biological activity and bioavailability without increasing toxicity. EF24 exerts antitumor activity by arresting the cell cycle and inducing apoptosis, suppressing many types of cancer cells in vitro. The antiproliferative and antiangiogenic properties of EF24 provide theoretical support for its development and application to liver cancers. We investigated the in vitro and in vivo activities of EF24 on liver cancer to better understand its therapeutic effects and mechanisms. EF24 induced significant apoptosis and G2/M-phase cell cycle arrest in mouse liver cancer cell lines, Hepa1-6 and H22. The expression levels of G2/M cell cycle regulating factors, cyclin B1 and Cdc2, were significantly decreased, pp53, p53, and p21 were significantly increased in EF24-treated cells. In addition, EF24 treatment significantly reduced Bcl-2 concomitant with an increase in Bax, enhanced the release of cytochrome c from the mitochondria into the cytosol, resulting in an upregulation of cleaved-caspase-3, which promoted poly (ADP-ribose) polymerase cleavage. EF24-treated cells also displayed decreases in phosphorylated Akt, phosphorylated extracellular signal-regulated kinase and vascular endothelial growth factor. Our in vitro protein expression data were confirmed in vivo using a subcutaneous hepatocellular carcinoma (HCC) tumor model. This mouse HCC model confirmed that total body weight was unchanged following EF24 treatment, although tumor weight was significantly decreased. Using an orthotopic HCC model, EF24 significantly reduced the liver/body weight ratio and relative tumor areas compared to the control group. In situ detection of apoptotic cells and quantification of Ki-67, a biomarker of cell proliferation, all indicated significant tumor suppression with EF24 treatment. These results suggest that EF24 exhibits anti-tumor activity on liver cancer cells via mitochondria-dependent apoptosis and inducing cell cycle arrest coupled with antiangiogenesis. The demonstrated activities of EF24 support its further evaluation as a treatment for human liver cancers.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23118928</pmid><doi>10.1371/journal.pone.0048075</doi><tpages>e48075</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-10, Vol.7 (10), p.e48075-e48075 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1326562427 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenosine diphosphate AKT protein Angiogenesis Inhibitors - pharmacology Animals Antiangiogenics Anticancer properties Antitumor activity Antitumor agents Apoptosis Apoptosis - drug effects Bax protein Bcl-2 protein Benzylidene Compounds - pharmacology Bioavailability Biocompatibility Biological activity Biology Biomarkers Body weight Cancer Carcinoma, Hepatocellular - blood supply Carcinoma, Hepatocellular - drug therapy Carcinoma, Hepatocellular - pathology Caspase Caspase-3 Cdc2 protein Cell cycle Cell Cycle Checkpoints - drug effects Cell growth Cell Line, Tumor Cell proliferation Cell Proliferation - drug effects Cell Survival - drug effects Curcumin Cyclin B1 Cytochrome Cytochrome c Cytosol Data processing Extracellular signal-regulated kinase Health aspects Hepatocellular carcinoma Hepatocytes Humans In vivo methods and tests Kinases Liver Liver cancer Liver Neoplasms, Experimental - blood supply Liver Neoplasms, Experimental - drug therapy Liver Neoplasms, Experimental - pathology Male MAP Kinase Signaling System - drug effects Medicine Mice Mice, Inbred C57BL Mitochondria Piperidones - pharmacology Ribose Rodents Toxicity Tumor Burden - drug effects Tumor cell lines Tumor proteins Tumor suppression Ubiquitin-Protein Ligases - drug effects Ubiquitin-Protein Ligases - physiology Vascular endothelial growth factor Weight reduction Xenograft Model Antitumor Assays |
| title | In vivo and in vitro suppression of hepatocellular carcinoma by EF24, a curcumin analog |
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