Cytotoxic Effect of a Novel Synthesized Carbazole Compound on A549 Lung Cancer Cell Line
Increased death rates due to lung cancer have necessitated the search for potential novel anticancer compounds such as carbazole derivatives. Carbazoles are aromatic heterocyclic compounds with anticancer, antibacterial and anti-inflammatory activity. The study investigated the ability of the novel...
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| creator | Molatlhegi, Refilwe P Phulukdaree, Alisa Anand, Krishnan Gengan, Robert M Tiloke, Charlette Chuturgoon, Anil A |
| description | Increased death rates due to lung cancer have necessitated the search for potential novel anticancer compounds such as carbazole derivatives. Carbazoles are aromatic heterocyclic compounds with anticancer, antibacterial and anti-inflammatory activity. The study investigated the ability of the novel carbazole compound (Z)-4-[9-ethyl-9aH-carbazol-3-yl) amino] pent-3-en-2-one (ECAP) to induce cytotoxicity of lung cancer cells and its mechanism of action. ECAP was synthesized as a yellow powder with melting point of 240-247 °C. The 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lipid peroxidation and comet assays were used to assess the cytotoxic effect of the compound on A549 lung cancer cells. Protein expression was determined using western blots, apoptosis was measured by luminometry (caspase-3/7, -8 and -9) assay and flow cytometry was used to measure phosphatidylserine (PS) externalisation. ECAP induced a p53 mediated apoptosis of lung cancer cells due to a significant reduction in the expression of antioxidant defence proteins (Nrf2 and SOD), Hsp70 (p < 0.02) and Bcl-2 (p < 0.0006), thereby up-regulating reactive oxygen species (ROS) production. This resulted in DNA damage (p < 0.0001), up-regulation of Bax expression and caspase activity and induction of apoptosis in lung cancer cells. The results show the anticancer potential of ECAP on lung cancer. |
| doi_str_mv | 10.1371/journal.pone.0129874 |
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Carbazoles are aromatic heterocyclic compounds with anticancer, antibacterial and anti-inflammatory activity. The study investigated the ability of the novel carbazole compound (Z)-4-[9-ethyl-9aH-carbazol-3-yl) amino] pent-3-en-2-one (ECAP) to induce cytotoxicity of lung cancer cells and its mechanism of action. ECAP was synthesized as a yellow powder with melting point of 240-247 °C. The 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lipid peroxidation and comet assays were used to assess the cytotoxic effect of the compound on A549 lung cancer cells. Protein expression was determined using western blots, apoptosis was measured by luminometry (caspase-3/7, -8 and -9) assay and flow cytometry was used to measure phosphatidylserine (PS) externalisation. ECAP induced a p53 mediated apoptosis of lung cancer cells due to a significant reduction in the expression of antioxidant defence proteins (Nrf2 and SOD), Hsp70 (p < 0.02) and Bcl-2 (p < 0.0006), thereby up-regulating reactive oxygen species (ROS) production. This resulted in DNA damage (p < 0.0001), up-regulation of Bax expression and caspase activity and induction of apoptosis in lung cancer cells. The results show the anticancer potential of ECAP on lung cancer.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0129874</identifier><identifier>PMID: 26134408</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alternative medicine ; Anti-inflammatory agents ; Antibacterial materials ; Anticancer properties ; Antioxidants ; Apoptosis ; Apoptosis - drug effects ; Aromatic compounds ; BAX protein ; Bcl-2 protein ; bcl-2-Associated X Protein - agonists ; bcl-2-Associated X Protein - genetics ; bcl-2-Associated X Protein - metabolism ; Bioassay ; Bioassays ; Biochemistry ; Cancer ; Carbazole ; Carbazoles ; Carbazoles - chemical synthesis ; Carbazoles - pharmacology ; Caspase ; Caspase-3 ; Caspases - genetics ; Caspases - metabolism ; Cell cycle ; Cell death ; Cell growth ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Cytometry ; Cytotoxicity ; Cytotoxins - chemical synthesis ; Cytotoxins - pharmacology ; Damage detection ; Deoxyribonucleic acid ; Developing countries ; Discipline ; DNA ; DNA damage ; Epithelial Cells - drug effects ; Epithelial Cells - metabolism ; Epithelial Cells - pathology ; Equal channel angular pressing ; Flow cytometry ; Gene expression ; Gene Expression Regulation, Neoplastic ; Heat shock proteins ; Heterocyclic compounds ; Homeostasis ; HSP70 Heat-Shock Proteins - antagonists & inhibitors ; HSP70 Heat-Shock Proteins - genetics ; HSP70 Heat-Shock Proteins - metabolism ; Hsp70 protein ; Humans ; Inflammation ; Laboratories ; LDCs ; Lipid Peroxidation ; Lung cancer ; Lung diseases ; Melting point ; Mortality ; NF-E2-Related Factor 2 - antagonists & inhibitors ; NF-E2-Related Factor 2 - genetics ; NF-E2-Related Factor 2 - metabolism ; Oxidative stress ; Oxidative Stress - drug effects ; Oxygen ; p53 Protein ; Pentanones - chemical synthesis ; Pentanones - pharmacology ; Peroxidation ; Pharmaceutical sciences ; Phosphatidylserine ; Phosphatidylserines - metabolism ; Powder ; Proteins ; Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors ; Proto-Oncogene Proteins c-bcl-2 - genetics ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Reactive oxygen species ; Reactive Oxygen Species - agonists ; Reactive Oxygen Species - metabolism ; Respiratory Mucosa - drug effects ; Respiratory Mucosa - metabolism ; Respiratory Mucosa - pathology ; Signal Transduction ; Superoxide Dismutase - antagonists & inhibitors ; Superoxide Dismutase - genetics ; Superoxide Dismutase - metabolism ; Synthesis ; Toxicity ; Tumor proteins ; Tumor Suppressor Protein p53 - antagonists & inhibitors ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - metabolism ; Western blotting</subject><ispartof>PloS one, 2015-07, Vol.10 (7), p.e0129874</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Molatlhegi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://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>2015 Molatlhegi et al 2015 Molatlhegi et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-6b52df3077ada8bcc896a0e908b3dc3ebb05f253fee33f198efddd21274fab373</citedby><cites>FETCH-LOGICAL-c692t-6b52df3077ada8bcc896a0e908b3dc3ebb05f253fee33f198efddd21274fab373</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/PMC4489925/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4489925/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26134408$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Molatlhegi, Refilwe P</creatorcontrib><creatorcontrib>Phulukdaree, Alisa</creatorcontrib><creatorcontrib>Anand, Krishnan</creatorcontrib><creatorcontrib>Gengan, Robert M</creatorcontrib><creatorcontrib>Tiloke, Charlette</creatorcontrib><creatorcontrib>Chuturgoon, Anil A</creatorcontrib><title>Cytotoxic Effect of a Novel Synthesized Carbazole Compound on A549 Lung Cancer Cell Line</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Increased death rates due to lung cancer have necessitated the search for potential novel anticancer compounds such as carbazole derivatives. Carbazoles are aromatic heterocyclic compounds with anticancer, antibacterial and anti-inflammatory activity. The study investigated the ability of the novel carbazole compound (Z)-4-[9-ethyl-9aH-carbazol-3-yl) amino] pent-3-en-2-one (ECAP) to induce cytotoxicity of lung cancer cells and its mechanism of action. ECAP was synthesized as a yellow powder with melting point of 240-247 °C. The 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lipid peroxidation and comet assays were used to assess the cytotoxic effect of the compound on A549 lung cancer cells. Protein expression was determined using western blots, apoptosis was measured by luminometry (caspase-3/7, -8 and -9) assay and flow cytometry was used to measure phosphatidylserine (PS) externalisation. ECAP induced a p53 mediated apoptosis of lung cancer cells due to a significant reduction in the expression of antioxidant defence proteins (Nrf2 and SOD), Hsp70 (p < 0.02) and Bcl-2 (p < 0.0006), thereby up-regulating reactive oxygen species (ROS) production. This resulted in DNA damage (p < 0.0001), up-regulation of Bax expression and caspase activity and induction of apoptosis in lung cancer cells. The results show the anticancer potential of ECAP on lung cancer.</description><subject>Alternative medicine</subject><subject>Anti-inflammatory agents</subject><subject>Antibacterial materials</subject><subject>Anticancer properties</subject><subject>Antioxidants</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Aromatic compounds</subject><subject>BAX protein</subject><subject>Bcl-2 protein</subject><subject>bcl-2-Associated X Protein - agonists</subject><subject>bcl-2-Associated X Protein - genetics</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>Bioassay</subject><subject>Bioassays</subject><subject>Biochemistry</subject><subject>Cancer</subject><subject>Carbazole</subject><subject>Carbazoles</subject><subject>Carbazoles - chemical synthesis</subject><subject>Carbazoles - pharmacology</subject><subject>Caspase</subject><subject>Caspase-3</subject><subject>Caspases - genetics</subject><subject>Caspases - metabolism</subject><subject>Cell cycle</subject><subject>Cell death</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Cytometry</subject><subject>Cytotoxicity</subject><subject>Cytotoxins - chemical synthesis</subject><subject>Cytotoxins - pharmacology</subject><subject>Damage detection</subject><subject>Deoxyribonucleic acid</subject><subject>Developing countries</subject><subject>Discipline</subject><subject>DNA</subject><subject>DNA damage</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelial Cells - pathology</subject><subject>Equal channel angular pressing</subject><subject>Flow cytometry</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Heat shock proteins</subject><subject>Heterocyclic compounds</subject><subject>Homeostasis</subject><subject>HSP70 Heat-Shock Proteins - antagonists & inhibitors</subject><subject>HSP70 Heat-Shock Proteins - genetics</subject><subject>HSP70 Heat-Shock Proteins - metabolism</subject><subject>Hsp70 protein</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Laboratories</subject><subject>LDCs</subject><subject>Lipid Peroxidation</subject><subject>Lung cancer</subject><subject>Lung diseases</subject><subject>Melting point</subject><subject>Mortality</subject><subject>NF-E2-Related Factor 2 - antagonists & inhibitors</subject><subject>NF-E2-Related Factor 2 - genetics</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Oxygen</subject><subject>p53 Protein</subject><subject>Pentanones - chemical synthesis</subject><subject>Pentanones - pharmacology</subject><subject>Peroxidation</subject><subject>Pharmaceutical sciences</subject><subject>Phosphatidylserine</subject><subject>Phosphatidylserines - metabolism</subject><subject>Powder</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - agonists</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Respiratory Mucosa - drug effects</subject><subject>Respiratory Mucosa - metabolism</subject><subject>Respiratory Mucosa - pathology</subject><subject>Signal Transduction</subject><subject>Superoxide Dismutase - antagonists & inhibitors</subject><subject>Superoxide Dismutase - genetics</subject><subject>Superoxide Dismutase - metabolism</subject><subject>Synthesis</subject><subject>Toxicity</subject><subject>Tumor proteins</subject><subject>Tumor Suppressor Protein p53 - antagonists & inhibitors</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Western blotting</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk99v0zAQxyMEYmPwHyCIhITgocW_4tgvSFU0oFLFJAaIN8txzm2q1O7iZFr31-Ou2dSgPSA_2Lr73Pd8Z1-SvMZoimmOP6193zrdTLfewRRhIkXOniSnWFIy4QTRp0fnk-RFCGuEMio4f56cEI4pY0icJn-KXec7f1Ob9NxaMF3qbarT7_4amvRy57oVhPoWqrTQbalvfQNp4Tdb37sq9S6dZUymi94to98ZaNMCmiZd1A5eJs-sbgK8Gvaz5NeX85_Ft8ni4uu8mC0mhkvSTXiZkcpSlOe60qI0RkiuEUgkSloZCmWJMksyagEotVgKsFVVEUxyZnVJc3qWvD3obhsf1NCUoDCXFAuJpIzE_EBUXq_Vtq03ut0pr2t1Z_DtUum2q00DihoJhOFSc8FZaUHkpQFBSoJAE8101Po8ZOvLDVQGXNfqZiQ69rh6pZb-WjEmpIx1nCUfBoHWX_UQOrWpg4lN0w58f3dvJjlHco---wd9vLqBWupYQO2sj3nNXlTNGEFE5DTDkZo-QsVVwaY28QfZOtpHAR9HAZHp4KZb6j4ENb_88f_sxe8x-_6IXYFuulXwTd_V3oUxyA6gaX0ILdiHJmOk9gNw3w21HwA1DEAMe3P8QA9B9z-e_gU_X_-0</recordid><startdate>20150702</startdate><enddate>20150702</enddate><creator>Molatlhegi, Refilwe P</creator><creator>Phulukdaree, Alisa</creator><creator>Anand, Krishnan</creator><creator>Gengan, Robert M</creator><creator>Tiloke, Charlette</creator><creator>Chuturgoon, Anil A</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>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</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>20150702</creationdate><title>Cytotoxic Effect of a Novel Synthesized Carbazole Compound on A549 Lung Cancer Cell Line</title><author>Molatlhegi, Refilwe P ; Phulukdaree, Alisa ; Anand, Krishnan ; Gengan, Robert M ; Tiloke, Charlette ; Chuturgoon, Anil A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-6b52df3077ada8bcc896a0e908b3dc3ebb05f253fee33f198efddd21274fab373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Alternative medicine</topic><topic>Anti-inflammatory agents</topic><topic>Antibacterial materials</topic><topic>Anticancer properties</topic><topic>Antioxidants</topic><topic>Apoptosis</topic><topic>Apoptosis - 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drug effects</topic><topic>Oxygen</topic><topic>p53 Protein</topic><topic>Pentanones - chemical synthesis</topic><topic>Pentanones - pharmacology</topic><topic>Peroxidation</topic><topic>Pharmaceutical sciences</topic><topic>Phosphatidylserine</topic><topic>Phosphatidylserines - metabolism</topic><topic>Powder</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors</topic><topic>Proto-Oncogene Proteins c-bcl-2 - genetics</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Reactive oxygen species</topic><topic>Reactive Oxygen Species - agonists</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Respiratory Mucosa - drug effects</topic><topic>Respiratory Mucosa - metabolism</topic><topic>Respiratory Mucosa - pathology</topic><topic>Signal Transduction</topic><topic>Superoxide Dismutase - antagonists & inhibitors</topic><topic>Superoxide Dismutase - genetics</topic><topic>Superoxide Dismutase - metabolism</topic><topic>Synthesis</topic><topic>Toxicity</topic><topic>Tumor proteins</topic><topic>Tumor Suppressor Protein p53 - antagonists & inhibitors</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Molatlhegi, Refilwe P</creatorcontrib><creatorcontrib>Phulukdaree, Alisa</creatorcontrib><creatorcontrib>Anand, Krishnan</creatorcontrib><creatorcontrib>Gengan, Robert M</creatorcontrib><creatorcontrib>Tiloke, Charlette</creatorcontrib><creatorcontrib>Chuturgoon, Anil A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</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>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</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>Molatlhegi, Refilwe P</au><au>Phulukdaree, Alisa</au><au>Anand, Krishnan</au><au>Gengan, Robert M</au><au>Tiloke, Charlette</au><au>Chuturgoon, Anil A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytotoxic Effect of a Novel Synthesized Carbazole Compound on A549 Lung Cancer Cell Line</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-07-02</date><risdate>2015</risdate><volume>10</volume><issue>7</issue><spage>e0129874</spage><pages>e0129874-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Increased death rates due to lung cancer have necessitated the search for potential novel anticancer compounds such as carbazole derivatives. Carbazoles are aromatic heterocyclic compounds with anticancer, antibacterial and anti-inflammatory activity. The study investigated the ability of the novel carbazole compound (Z)-4-[9-ethyl-9aH-carbazol-3-yl) amino] pent-3-en-2-one (ECAP) to induce cytotoxicity of lung cancer cells and its mechanism of action. ECAP was synthesized as a yellow powder with melting point of 240-247 °C. The 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lipid peroxidation and comet assays were used to assess the cytotoxic effect of the compound on A549 lung cancer cells. Protein expression was determined using western blots, apoptosis was measured by luminometry (caspase-3/7, -8 and -9) assay and flow cytometry was used to measure phosphatidylserine (PS) externalisation. ECAP induced a p53 mediated apoptosis of lung cancer cells due to a significant reduction in the expression of antioxidant defence proteins (Nrf2 and SOD), Hsp70 (p < 0.02) and Bcl-2 (p < 0.0006), thereby up-regulating reactive oxygen species (ROS) production. This resulted in DNA damage (p < 0.0001), up-regulation of Bax expression and caspase activity and induction of apoptosis in lung cancer cells. The results show the anticancer potential of ECAP on lung cancer.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26134408</pmid><doi>10.1371/journal.pone.0129874</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-07, Vol.10 (7), p.e0129874 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1693189099 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Alternative medicine Anti-inflammatory agents Antibacterial materials Anticancer properties Antioxidants Apoptosis Apoptosis - drug effects Aromatic compounds BAX protein Bcl-2 protein bcl-2-Associated X Protein - agonists bcl-2-Associated X Protein - genetics bcl-2-Associated X Protein - metabolism Bioassay Bioassays Biochemistry Cancer Carbazole Carbazoles Carbazoles - chemical synthesis Carbazoles - pharmacology Caspase Caspase-3 Caspases - genetics Caspases - metabolism Cell cycle Cell death Cell growth Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects Cytometry Cytotoxicity Cytotoxins - chemical synthesis Cytotoxins - pharmacology Damage detection Deoxyribonucleic acid Developing countries Discipline DNA DNA damage Epithelial Cells - drug effects Epithelial Cells - metabolism Epithelial Cells - pathology Equal channel angular pressing Flow cytometry Gene expression Gene Expression Regulation, Neoplastic Heat shock proteins Heterocyclic compounds Homeostasis HSP70 Heat-Shock Proteins - antagonists & inhibitors HSP70 Heat-Shock Proteins - genetics HSP70 Heat-Shock Proteins - metabolism Hsp70 protein Humans Inflammation Laboratories LDCs Lipid Peroxidation Lung cancer Lung diseases Melting point Mortality NF-E2-Related Factor 2 - antagonists & inhibitors NF-E2-Related Factor 2 - genetics NF-E2-Related Factor 2 - metabolism Oxidative stress Oxidative Stress - drug effects Oxygen p53 Protein Pentanones - chemical synthesis Pentanones - pharmacology Peroxidation Pharmaceutical sciences Phosphatidylserine Phosphatidylserines - metabolism Powder Proteins Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-bcl-2 - metabolism Reactive oxygen species Reactive Oxygen Species - agonists Reactive Oxygen Species - metabolism Respiratory Mucosa - drug effects Respiratory Mucosa - metabolism Respiratory Mucosa - pathology Signal Transduction Superoxide Dismutase - antagonists & inhibitors Superoxide Dismutase - genetics Superoxide Dismutase - metabolism Synthesis Toxicity Tumor proteins Tumor Suppressor Protein p53 - antagonists & inhibitors Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Western blotting |
| title | Cytotoxic Effect of a Novel Synthesized Carbazole Compound on A549 Lung Cancer Cell Line |
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