Anti-Cancer Activity of a 5-Aminopyrazole Derivative Lead Compound (BC-7) and Potential Synergistic Cytotoxicity with Cisplatin against Human Cervical Cancer Cells
Identifieur interne : 000A83 ( Main/Exploration ); précédent : 000A82; suivant : 000A84Anti-Cancer Activity of a 5-Aminopyrazole Derivative Lead Compound (BC-7) and Potential Synergistic Cytotoxicity with Cisplatin against Human Cervical Cancer Cells
Auteurs : Bresler Swanepoel ; George Mihai Nitulescu ; Octavian Tudorel Olaru ; Luanne Venables ; Maryna Van De VenterSource :
- International Journal of Molecular Sciences [ 1422-0067 ] ; 2019.
Abstract
The use of some very well-known chemotherapeutic agents, such as cisplatin, is limited by toxicity in normal tissues and the development of drug resistance. In order to address drug resistance and the side-effects of anti-cancer agents, recent research has focused on finding novel combinations of anti-cancer agents with non-overlapping mechanisms of action. The cytotoxic effect of the synthetic 5-aminopyrazole derivative
Url:
DOI: 10.3390/ijms20225559
PubMed: 31703393
PubMed Central: 6888365
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Anti-Cancer Activity of a 5-Aminopyrazole Derivative Lead Compound (BC-7) and Potential Synergistic Cytotoxicity with Cisplatin against Human Cervical Cancer Cells</title><author><name sortKey="Swanepoel, Bresler" sort="Swanepoel, Bresler" uniqKey="Swanepoel B" first="Bresler" last="Swanepoel">Bresler Swanepoel</name><affiliation><nlm:aff id="af1-ijms-20-05559">Department of Biochemistry and Microbiology, Nelson Mandela University, P.O. Box 77000, Port Elizabeth 6031, South Africa;<email>s211129399@mandela.ac.za</email> (B.S.);<email>s204004039@mandela.ac.za</email> (L.V.);<email>Maryna.VanDeVenter@mandela.ac.za</email> (M.v.d.V.)</nlm:aff></affiliation></author><author><name sortKey="Nitulescu, George Mihai" sort="Nitulescu, George Mihai" uniqKey="Nitulescu G" first="George Mihai" last="Nitulescu">George Mihai Nitulescu</name><affiliation><nlm:aff id="af2-ijms-20-05559">Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, Romania;<email>octavian.olaru@umfcd.ro</email></nlm:aff></affiliation></author><author><name sortKey="Olaru, Octavian Tudorel" sort="Olaru, Octavian Tudorel" uniqKey="Olaru O" first="Octavian Tudorel" last="Olaru">Octavian Tudorel Olaru</name><affiliation><nlm:aff id="af2-ijms-20-05559">Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, Romania;<email>octavian.olaru@umfcd.ro</email></nlm:aff></affiliation></author><author><name sortKey="Venables, Luanne" sort="Venables, Luanne" uniqKey="Venables L" first="Luanne" last="Venables">Luanne Venables</name><affiliation><nlm:aff id="af1-ijms-20-05559">Department of Biochemistry and Microbiology, Nelson Mandela University, P.O. Box 77000, Port Elizabeth 6031, South Africa;<email>s211129399@mandela.ac.za</email> (B.S.);<email>s204004039@mandela.ac.za</email> (L.V.);<email>Maryna.VanDeVenter@mandela.ac.za</email> (M.v.d.V.)</nlm:aff></affiliation></author><author><name sortKey="Van De Venter, Maryna" sort="Van De Venter, Maryna" uniqKey="Van De Venter M" first="Maryna" last="Van De Venter">Maryna Van De Venter</name><affiliation><nlm:aff id="af1-ijms-20-05559">Department of Biochemistry and Microbiology, Nelson Mandela University, P.O. Box 77000, Port Elizabeth 6031, South Africa;<email>s211129399@mandela.ac.za</email> (B.S.);<email>s204004039@mandela.ac.za</email> (L.V.);<email>Maryna.VanDeVenter@mandela.ac.za</email> (M.v.d.V.)</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31703393</idno><idno type="pmc">6888365</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888365</idno><idno type="RBID">PMC:6888365</idno><idno type="doi">10.3390/ijms20225559</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000616</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000616</idno><idno type="wicri:Area/Pmc/Curation">000616</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000616</idno><idno type="wicri:Area/Pmc/Checkpoint">000A09</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000A09</idno><idno type="wicri:Area/Ncbi/Merge">000B88</idno><idno type="wicri:Area/Ncbi/Curation">000B88</idno><idno type="wicri:Area/Ncbi/Checkpoint">000B88</idno><idno type="wicri:Area/Main/Merge">000A83</idno><idno type="wicri:Area/Main/Curation">000A83</idno><idno type="wicri:Area/Main/Exploration">000A83</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Anti-Cancer Activity of a 5-Aminopyrazole Derivative Lead Compound (BC-7) and Potential Synergistic Cytotoxicity with Cisplatin against Human Cervical Cancer Cells</title><author><name sortKey="Swanepoel, Bresler" sort="Swanepoel, Bresler" uniqKey="Swanepoel B" first="Bresler" last="Swanepoel">Bresler Swanepoel</name><affiliation><nlm:aff id="af1-ijms-20-05559">Department of Biochemistry and Microbiology, Nelson Mandela University, P.O. Box 77000, Port Elizabeth 6031, South Africa;<email>s211129399@mandela.ac.za</email> (B.S.);<email>s204004039@mandela.ac.za</email> (L.V.);<email>Maryna.VanDeVenter@mandela.ac.za</email> (M.v.d.V.)</nlm:aff></affiliation></author><author><name sortKey="Nitulescu, George Mihai" sort="Nitulescu, George Mihai" uniqKey="Nitulescu G" first="George Mihai" last="Nitulescu">George Mihai Nitulescu</name><affiliation><nlm:aff id="af2-ijms-20-05559">Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, Romania;<email>octavian.olaru@umfcd.ro</email></nlm:aff></affiliation></author><author><name sortKey="Olaru, Octavian Tudorel" sort="Olaru, Octavian Tudorel" uniqKey="Olaru O" first="Octavian Tudorel" last="Olaru">Octavian Tudorel Olaru</name><affiliation><nlm:aff id="af2-ijms-20-05559">Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, Romania;<email>octavian.olaru@umfcd.ro</email></nlm:aff></affiliation></author><author><name sortKey="Venables, Luanne" sort="Venables, Luanne" uniqKey="Venables L" first="Luanne" last="Venables">Luanne Venables</name><affiliation><nlm:aff id="af1-ijms-20-05559">Department of Biochemistry and Microbiology, Nelson Mandela University, P.O. Box 77000, Port Elizabeth 6031, South Africa;<email>s211129399@mandela.ac.za</email> (B.S.);<email>s204004039@mandela.ac.za</email> (L.V.);<email>Maryna.VanDeVenter@mandela.ac.za</email> (M.v.d.V.)</nlm:aff></affiliation></author><author><name sortKey="Van De Venter, Maryna" sort="Van De Venter, Maryna" uniqKey="Van De Venter M" first="Maryna" last="Van De Venter">Maryna Van De Venter</name><affiliation><nlm:aff id="af1-ijms-20-05559">Department of Biochemistry and Microbiology, Nelson Mandela University, P.O. Box 77000, Port Elizabeth 6031, South Africa;<email>s211129399@mandela.ac.za</email> (B.S.);<email>s204004039@mandela.ac.za</email> (L.V.);<email>Maryna.VanDeVenter@mandela.ac.za</email> (M.v.d.V.)</nlm:aff></affiliation></author></analytic><series><title level="j">International Journal of Molecular Sciences</title><idno type="eISSN">1422-0067</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The use of some very well-known chemotherapeutic agents, such as cisplatin, is limited by toxicity in normal tissues and the development of drug resistance. In order to address drug resistance and the side-effects of anti-cancer agents, recent research has focused on finding novel combinations of anti-cancer agents with non-overlapping mechanisms of action. The cytotoxic effect of the synthetic 5-aminopyrazole derivative <italic>N</italic>-[[3-(4-bromophenyl)-1<italic>H</italic>-pyrazol-5-yl]-carbamothioyl]-4-chloro-benzamide (BC-7) was evaluated by the bis-Benzamide H 33342 trihydrochloride/propidium iodide (Hoechst 33342/PI) dual staining method against HeLa, MeWo, HepG2, Vero, and MRHF cell lines. Quantitative fluorescence image analysis was used for the elucidation of mechanism of action and synergism with cisplatin in HeLa cells. BC-7 displayed selective cytotoxicity towards HeLa cells (IC<sub>50</sub> 65.58 ± 8.40 μM) and induced apoptosis in a mitochondrial- and caspase dependent manner. This was most likely preceded by cell cycle arrest in the early M phase and the onset of mitotic catastrophe. BC-7 increased the cytotoxic effect of cisplatin in a synergistic manner with combination index (CI) values less than 0.9 accompanied by highly favourable dose reduction indices. Therefore, the results obtained support the implication that BC-7 has potential anti-cancer properties and that combinations of BC-7 with cisplatin should be further investigated for potential clinical applications.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Gatta, G" uniqKey="Gatta G">G. Gatta</name></author><author><name sortKey="Zigon, G" uniqKey="Zigon G">G. Zigon</name></author><author><name sortKey="Capocaccia, R" uniqKey="Capocaccia R">R. Capocaccia</name></author><author><name sortKey="Coebergh, J W" uniqKey="Coebergh J">J.W. Coebergh</name></author><author><name sortKey="Desandes, E" uniqKey="Desandes E">E. Desandes</name></author><author><name sortKey="Kaatsch, P" uniqKey="Kaatsch P">P. Kaatsch</name></author><author><name sortKey="Pastore, G" uniqKey="Pastore G">G. Pastore</name></author><author><name sortKey="Peris Bonet, R" uniqKey="Peris Bonet R">R. 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Hsu</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="Nitulescu, George Mihai" sort="Nitulescu, George Mihai" uniqKey="Nitulescu G" first="George Mihai" last="Nitulescu">George Mihai Nitulescu</name><name sortKey="Olaru, Octavian Tudorel" sort="Olaru, Octavian Tudorel" uniqKey="Olaru O" first="Octavian Tudorel" last="Olaru">Octavian Tudorel Olaru</name><name sortKey="Swanepoel, Bresler" sort="Swanepoel, Bresler" uniqKey="Swanepoel B" first="Bresler" last="Swanepoel">Bresler Swanepoel</name><name sortKey="Van De Venter, Maryna" sort="Van De Venter, Maryna" uniqKey="Van De Venter M" first="Maryna" last="Van De Venter">Maryna Van De Venter</name><name sortKey="Venables, Luanne" sort="Venables, Luanne" uniqKey="Venables L" first="Luanne" last="Venables">Luanne Venables</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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