(S)-Goniothalamin induces DNA damage, apoptosis, and decrease in BIRC5 messenger RNA levels in NCI-H460 cells
(R)-Goniothalamin (R-GNT) is a secondary metabolite isolated from the plants of the genus Goniothalamus. This molecule has attracted the attention of researchers because of its selective cytotoxicity against tumor cells and its ability to induce apoptosis. (S)-Goniothalamin (S-GNT) is a synthetic en...
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| Veröffentlicht in: | Human & experimental toxicology 2014-01, Vol.33 (1), p.3-13 |
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| creator | Semprebon, SC de Fátima, Â Lepri, SR Sartori, D Ribeiro, LR Mantovani, MS |
| description | (R)-Goniothalamin (R-GNT) is a secondary metabolite isolated from the plants of the genus Goniothalamus. This molecule has attracted the attention of researchers because of its selective cytotoxicity against tumor cells and its ability to induce apoptosis. (S)-Goniothalamin (S-GNT) is a synthetic enantiomer of R-GNT, and its mechanism of action is largely unknown. In this study, we investigated the activity of S-GNT in a human non-small cell lung cancer NCI-H460 cells. We observed that the cells exposed to this compound exhibited cytotoxicity in a concentration-dependent manner. Based on the data obtained through the assessment of apoptosis induction in situ and the comet assay, we suggest that this cytotoxicity occurs due to the potential ability of this molecule to induce DNA damage with the consequent induction of cell death via apoptosis. A significant reduction in the messenger RNA levels of baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) gene that encodes the survivin protein was found. This novel finding may explain the inhibition of cell proliferation and induction of apoptosis in tumor cells caused by this compound. |
| doi_str_mv | 10.1177/0960327113491506 |
| format | Article |
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This molecule has attracted the attention of researchers because of its selective cytotoxicity against tumor cells and its ability to induce apoptosis. (S)-Goniothalamin (S-GNT) is a synthetic enantiomer of R-GNT, and its mechanism of action is largely unknown. In this study, we investigated the activity of S-GNT in a human non-small cell lung cancer NCI-H460 cells. We observed that the cells exposed to this compound exhibited cytotoxicity in a concentration-dependent manner. Based on the data obtained through the assessment of apoptosis induction in situ and the comet assay, we suggest that this cytotoxicity occurs due to the potential ability of this molecule to induce DNA damage with the consequent induction of cell death via apoptosis. A significant reduction in the messenger RNA levels of baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) gene that encodes the survivin protein was found. This novel finding may explain the inhibition of cell proliferation and induction of apoptosis in tumor cells caused by this compound.</description><identifier>ISSN: 0960-3271</identifier><identifier>EISSN: 1477-0903</identifier><identifier>DOI: 10.1177/0960327113491506</identifier><identifier>PMID: 23749456</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Antineoplastic Agents, Phytogenic - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Biological and medical sciences ; Cancer therapies ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Carcinoma, Non-Small-Cell Lung - metabolism ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Comet Assay ; DNA Damage ; Down-Regulation - drug effects ; Goniothalamus ; Humans ; Inhibitor of Apoptosis Proteins - antagonists & inhibitors ; Inhibitor of Apoptosis Proteins - genetics ; Inhibitor of Apoptosis Proteins - metabolism ; Kinetics ; Lethal Dose 50 ; Lung Neoplasms - drug therapy ; Lung Neoplasms - metabolism ; Medical sciences ; Neoplasm Proteins - antagonists & inhibitors ; Neoplasm Proteins - genetics ; Neoplasm Proteins - metabolism ; Pyrones - pharmacology ; RNA, Messenger - metabolism ; Stereoisomerism ; Studies ; Toxicology</subject><ispartof>Human & experimental toxicology, 2014-01, Vol.33 (1), p.3-13</ispartof><rights>The Author(s) 2014</rights><rights>2015 INIST-CNRS</rights><rights>SAGE Publications © Jan 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-248c19331466fca06a0ce77f2f6a8333da71065c38c7c46aa7a7e0d517466383</citedby><cites>FETCH-LOGICAL-c428t-248c19331466fca06a0ce77f2f6a8333da71065c38c7c46aa7a7e0d517466383</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/0960327113491506$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/0960327113491506$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,780,784,4022,21965,27852,27922,27923,27924,44944,45332</link.rule.ids><linktorsrc>$$Uhttps://journals.sagepub.com/doi/full/10.1177/0960327113491506?utm_source=summon&utm_medium=discovery-provider$$EView_record_in_SAGE_Publications$$FView_record_in_$$GSAGE_Publications</linktorsrc><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28522101$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23749456$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Semprebon, SC</creatorcontrib><creatorcontrib>de Fátima, Â</creatorcontrib><creatorcontrib>Lepri, SR</creatorcontrib><creatorcontrib>Sartori, D</creatorcontrib><creatorcontrib>Ribeiro, LR</creatorcontrib><creatorcontrib>Mantovani, MS</creatorcontrib><title>(S)-Goniothalamin induces DNA damage, apoptosis, and decrease in BIRC5 messenger RNA levels in NCI-H460 cells</title><title>Human & experimental toxicology</title><addtitle>Hum Exp Toxicol</addtitle><description>(R)-Goniothalamin (R-GNT) is a secondary metabolite isolated from the plants of the genus Goniothalamus. This molecule has attracted the attention of researchers because of its selective cytotoxicity against tumor cells and its ability to induce apoptosis. (S)-Goniothalamin (S-GNT) is a synthetic enantiomer of R-GNT, and its mechanism of action is largely unknown. In this study, we investigated the activity of S-GNT in a human non-small cell lung cancer NCI-H460 cells. We observed that the cells exposed to this compound exhibited cytotoxicity in a concentration-dependent manner. Based on the data obtained through the assessment of apoptosis induction in situ and the comet assay, we suggest that this cytotoxicity occurs due to the potential ability of this molecule to induce DNA damage with the consequent induction of cell death via apoptosis. A significant reduction in the messenger RNA levels of baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) gene that encodes the survivin protein was found. This novel finding may explain the inhibition of cell proliferation and induction of apoptosis in tumor cells caused by this compound.</description><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Biological and medical sciences</subject><subject>Cancer therapies</subject><subject>Carcinoma, Non-Small-Cell Lung - drug therapy</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Comet Assay</subject><subject>DNA Damage</subject><subject>Down-Regulation - drug effects</subject><subject>Goniothalamus</subject><subject>Humans</subject><subject>Inhibitor of Apoptosis Proteins - antagonists & inhibitors</subject><subject>Inhibitor of Apoptosis Proteins - genetics</subject><subject>Inhibitor of Apoptosis Proteins - metabolism</subject><subject>Kinetics</subject><subject>Lethal Dose 50</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - metabolism</subject><subject>Medical sciences</subject><subject>Neoplasm Proteins - antagonists & inhibitors</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Pyrones - pharmacology</subject><subject>RNA, Messenger - metabolism</subject><subject>Stereoisomerism</subject><subject>Studies</subject><subject>Toxicology</subject><issn>0960-3271</issn><issn>1477-0903</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kVtrFEEQhRtRzLr67pM0iBDB0erLdE8_xlWThRAh5n0oe2rihLmsXTuC_94edr0Q8KkazneqDn2EeK7grVLev4PgwGivlLFBleAeiJWy3hcQwDwUq0UuFv1EPGG-AwAXSvVYnGjjbbClW4nh9Mvr4nwau2n_DXsculF2YzNHYvnh6kw2OOAtvZG4m3b7iTvOz7GRDcVEyJRZ-X57vSnlQMw03lKS19nW0w_qeVGvNtviwjqQkfqen4pHLfZMz45zLW4-fbzZXBSXn8-3m7PLIlpd7Qttq6iCMco610YEhxDJ-1a3DitjTINegSujqaKP1iF69ARNqXw2mMqsxelh7S5N32fifT10vATAkaaZa2WDdtpr6zP68h56N81pzOEy5cGHKuQkawEHKqaJOVFb71I3YPpZK6iXJur7TWTLi-Pi-etAzR_D76_PwKsjgByxbxOOseO_XFVqrUBlrjhwnJv4J93_Dv8CAw6YXQ</recordid><startdate>201401</startdate><enddate>201401</enddate><creator>Semprebon, SC</creator><creator>de Fátima, Â</creator><creator>Lepri, SR</creator><creator>Sartori, D</creator><creator>Ribeiro, LR</creator><creator>Mantovani, MS</creator><general>SAGE Publications</general><general>Sage Publications</general><general>Sage Publications Ltd</general><scope>IQODW</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>7RV</scope><scope>7ST</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>AFKRA</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>SOI</scope><scope>7TM</scope></search><sort><creationdate>201401</creationdate><title>(S)-Goniothalamin induces DNA damage, apoptosis, and decrease in BIRC5 messenger RNA levels in NCI-H460 cells</title><author>Semprebon, SC ; 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This molecule has attracted the attention of researchers because of its selective cytotoxicity against tumor cells and its ability to induce apoptosis. (S)-Goniothalamin (S-GNT) is a synthetic enantiomer of R-GNT, and its mechanism of action is largely unknown. In this study, we investigated the activity of S-GNT in a human non-small cell lung cancer NCI-H460 cells. We observed that the cells exposed to this compound exhibited cytotoxicity in a concentration-dependent manner. Based on the data obtained through the assessment of apoptosis induction in situ and the comet assay, we suggest that this cytotoxicity occurs due to the potential ability of this molecule to induce DNA damage with the consequent induction of cell death via apoptosis. A significant reduction in the messenger RNA levels of baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) gene that encodes the survivin protein was found. This novel finding may explain the inhibition of cell proliferation and induction of apoptosis in tumor cells caused by this compound.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>23749456</pmid><doi>10.1177/0960327113491506</doi><tpages>11</tpages></addata></record> |
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| subjects | Antineoplastic Agents, Phytogenic - pharmacology Apoptosis Apoptosis - drug effects Biological and medical sciences Cancer therapies Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - metabolism Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects Comet Assay DNA Damage Down-Regulation - drug effects Goniothalamus Humans Inhibitor of Apoptosis Proteins - antagonists & inhibitors Inhibitor of Apoptosis Proteins - genetics Inhibitor of Apoptosis Proteins - metabolism Kinetics Lethal Dose 50 Lung Neoplasms - drug therapy Lung Neoplasms - metabolism Medical sciences Neoplasm Proteins - antagonists & inhibitors Neoplasm Proteins - genetics Neoplasm Proteins - metabolism Pyrones - pharmacology RNA, Messenger - metabolism Stereoisomerism Studies Toxicology |
| title | (S)-Goniothalamin induces DNA damage, apoptosis, and decrease in BIRC5 messenger RNA levels in NCI-H460 cells |
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