Crotoxin from Crotalus durissus terrificus venom: In vitro cytotoxic activity of a heterodimeric phospholipase A2 on human cancer-derived cell lines
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2018 |
| Outros Autores: | , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/1822/58207 |
Resumo: | Accepted manuscript |
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Crotoxin from Crotalus durissus terrificus venom: In vitro cytotoxic activity of a heterodimeric phospholipase A2 on human cancer-derived cell linesAmino Acid SequenceAnimalsAntineoplastic AgentsApoptosisCell CycleCell DeathCell Line, TumorCell SurvivalCrotalusCrotoxinHeLa CellsHumansInhibitory Concentration 50MiceNIH 3T3 CellsNeoplasmsPhospholipases A2Snake venomCytotoxicityAntitumorGliomaPancreasCiências Médicas::Medicina BásicaScience & TechnologyAccepted manuscriptCrotoxin (CTX), a heterodimeric phospholipase present in venom of snakes of the genus Crotalus, has demonstrated a broad spectrum of pharmacological properties, such as antimicrobial, hemostatic, and antitumoral. However, the precise mechanism of its cytotoxicity and antitumoral properties remains to be determined. Therefore, in the present study, we isolated crotoxin (F1 CTX) through two steps DEAE-Sepharose and Heparin-Sepharose FF chromatography. The C-terminal sequence of the A- and B-chain protein fragment was determined by LC-MS/MS mass spectrometry, which showed 100% identity to crotoxin structure. In order to investigate its cytotoxic effects, we demonstrated that the F1 CTX fraction at 0-30 μg/mL concentrations for 72 h presented a heterogeneous response profile on nine human cancer-derived cell lines from four tumor types (pancreatic, esophagus, cervical cancer, and glioma). The glioma (GAMG and HCB151) and pancreatic (PSN-1 and PANC-1) cancer cells showed a higher sensitivity with IC50 of <0.5, 4.1, 0.7 and < 0.5 μg/mL, respectively. Conversely, F1 CTX does not reduce the viability of normal cells. On the other hand, cervical (SiHa) and esophagus (KYSE270) cancer cell lines presented higher resistance, with IC50 higher than 30.2 and 8.7 μg/mL, respectively. Moreover, F1 CTX did not affect cell cycle distribution under the conditions evaluated and seems to be more cytotoxic than cytostatic. The pro-apoptotic effect of F1 CTX treatment was demonstrated in glioma (HCB151) cell line. In addition, crotoxin revealed a potential to initiate cell responses such as DNA damage in glioma (HCB151) and pancreatic cancer by H2AX activity induction. Conversely, F1 CTX does not reduce the viability of normal cells. Importantly, the comparison of F1 CTX effect with standard chemotherapeutic agents demonstrated a greater cytotoxic potential in the majority of tumor types (glioma, pancreatic, and cervical cancer). On the other hand, F1 CTX was less cytotoxic in esophageal cell lines compared to the gemcitabine agent used in clinical practice. Therefore, this work showed that F1 CTX has a cytotoxic activity and pro-apoptotic potential, contributing to the knowledge about the F1 crotoxin properties as well as its possible use in cancer research, particularly in glioma and pancreatic cancer cell lines.FAPESP, the Hermínio Ometto University Center, the Hospital de Cancer de Barretos and FINEP (MCTI/FINEP/MS/SCTIE/DECIT-01/2013 - FPXII-BIOPLAT). We acknowledge the Mass Spectrometry Laboratory of the Brazilian Biosciences National Laboratory, CNPEM, Campinas, Brazil, for providing support on mass spectrometry analysisinfo:eu-repo/semantics/publishedVersionPergamon-Elsevier Science LtdUniversidade do MinhoMuller, Silvana PinottiSilva, Viviane Aline OliveiraSilvestrini, Ana Vitória Pupode Macedo, Luana HenriqueCaetano, Guilherme FerreiraReis, R. M.Mazzi, Mauricio Ventura2018-12-152018-12-15T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/58207engMuller, S. P., Silva, V. A. O., Silvestrini, A. V. P., de Macedo, L. H., Caetano, G. F., Reis, R. M., & Mazzi, M. V. (2018). Crotoxin from Crotalus durissus terrificus venom: In vitro cytotoxic activity of a heterodimeric phospholipase A2 on human cancer-derived cell lines. Toxicon, 156, 13-220041-01011879-315010.1016/j.toxicon.2018.10.30630395843https://www.sciencedirect.com/science/article/pii/S0041010118307141info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:02:26Zoai:repositorium.sdum.uminho.pt:1822/58207Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:52:24.257609Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Crotoxin from Crotalus durissus terrificus venom: In vitro cytotoxic activity of a heterodimeric phospholipase A2 on human cancer-derived cell lines |
| title |
Crotoxin from Crotalus durissus terrificus venom: In vitro cytotoxic activity of a heterodimeric phospholipase A2 on human cancer-derived cell lines |
| spellingShingle |
Crotoxin from Crotalus durissus terrificus venom: In vitro cytotoxic activity of a heterodimeric phospholipase A2 on human cancer-derived cell lines Muller, Silvana Pinotti Amino Acid Sequence Animals Antineoplastic Agents Apoptosis Cell Cycle Cell Death Cell Line, Tumor Cell Survival Crotalus Crotoxin HeLa Cells Humans Inhibitory Concentration 50 Mice NIH 3T3 Cells Neoplasms Phospholipases A2 Snake venom Cytotoxicity Antitumor Glioma Pancreas Ciências Médicas::Medicina Básica Science & Technology |
| title_short |
Crotoxin from Crotalus durissus terrificus venom: In vitro cytotoxic activity of a heterodimeric phospholipase A2 on human cancer-derived cell lines |
| title_full |
Crotoxin from Crotalus durissus terrificus venom: In vitro cytotoxic activity of a heterodimeric phospholipase A2 on human cancer-derived cell lines |
| title_fullStr |
Crotoxin from Crotalus durissus terrificus venom: In vitro cytotoxic activity of a heterodimeric phospholipase A2 on human cancer-derived cell lines |
| title_full_unstemmed |
Crotoxin from Crotalus durissus terrificus venom: In vitro cytotoxic activity of a heterodimeric phospholipase A2 on human cancer-derived cell lines |
| title_sort |
Crotoxin from Crotalus durissus terrificus venom: In vitro cytotoxic activity of a heterodimeric phospholipase A2 on human cancer-derived cell lines |
| author |
Muller, Silvana Pinotti |
| author_facet |
Muller, Silvana Pinotti Silva, Viviane Aline Oliveira Silvestrini, Ana Vitória Pupo de Macedo, Luana Henrique Caetano, Guilherme Ferreira Reis, R. M. Mazzi, Mauricio Ventura |
| author_role |
author |
| author2 |
Silva, Viviane Aline Oliveira Silvestrini, Ana Vitória Pupo de Macedo, Luana Henrique Caetano, Guilherme Ferreira Reis, R. M. Mazzi, Mauricio Ventura |
| author2_role |
author author author author author author |
| dc.contributor.none.fl_str_mv |
Universidade do Minho |
| dc.contributor.author.fl_str_mv |
Muller, Silvana Pinotti Silva, Viviane Aline Oliveira Silvestrini, Ana Vitória Pupo de Macedo, Luana Henrique Caetano, Guilherme Ferreira Reis, R. M. Mazzi, Mauricio Ventura |
| dc.subject.por.fl_str_mv |
Amino Acid Sequence Animals Antineoplastic Agents Apoptosis Cell Cycle Cell Death Cell Line, Tumor Cell Survival Crotalus Crotoxin HeLa Cells Humans Inhibitory Concentration 50 Mice NIH 3T3 Cells Neoplasms Phospholipases A2 Snake venom Cytotoxicity Antitumor Glioma Pancreas Ciências Médicas::Medicina Básica Science & Technology |
| topic |
Amino Acid Sequence Animals Antineoplastic Agents Apoptosis Cell Cycle Cell Death Cell Line, Tumor Cell Survival Crotalus Crotoxin HeLa Cells Humans Inhibitory Concentration 50 Mice NIH 3T3 Cells Neoplasms Phospholipases A2 Snake venom Cytotoxicity Antitumor Glioma Pancreas Ciências Médicas::Medicina Básica Science & Technology |
| description |
Accepted manuscript |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018-12-15 2018-12-15T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/58207 |
| url |
http://hdl.handle.net/1822/58207 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Muller, S. P., Silva, V. A. O., Silvestrini, A. V. P., de Macedo, L. H., Caetano, G. F., Reis, R. M., & Mazzi, M. V. (2018). Crotoxin from Crotalus durissus terrificus venom: In vitro cytotoxic activity of a heterodimeric phospholipase A2 on human cancer-derived cell lines. Toxicon, 156, 13-22 0041-0101 1879-3150 10.1016/j.toxicon.2018.10.306 30395843 https://www.sciencedirect.com/science/article/pii/S0041010118307141 |
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info:eu-repo/semantics/openAccess |
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openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Pergamon-Elsevier Science Ltd |
| publisher.none.fl_str_mv |
Pergamon-Elsevier Science Ltd |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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