Exploring the safety of pllans-ii and antitumoral potential of its recombinant isoform in cervical cancer therapy
he antitumor potential of proteins from snake venoms has been studied in recent decades, and evidence has emerged that phospholipases A2 can selectively attack cells of various types of tumors. Previous results have shown that phospholipase A2 “Pllans-II,” isolated from Porthidium lansbergii lansber...
- Autores:
-
Sevilla-Sánchez, María José
Montoya-Gómez, Alejandro
Osorno-Valencia, Daniel
Mosquera-Escudero, Mildrey
Jiménez-Charris, Eliécer
Montealegre Sánchez, Leonel Ives
- Tipo de recurso:
- Article of investigation
- Fecha de publicación:
- 2023
- Institución:
- Universidad Autónoma de Occidente
- Repositorio:
- RED: Repositorio Educativo Digital UAO
- Idioma:
- eng
- OAI Identifier:
- oai:red.uao.edu.co:10614/15895
- Acceso en línea:
- https://hdl.handle.net/10614/15895
https://doi.org/10.3390/cells12242812
https://red.uao.edu.co/
- Palabra clave:
- Bioprospecting
Snake venom molecules
PLA2
Recombinant production
Drug discovery
Anticancer agents
- Rights
- openAccess
- License
- Derechos reservados - MDPI, 2023
| id |
REPOUAO2_1d07379211d8d195936a27eb5041c08c |
|---|---|
| oai_identifier_str |
oai:red.uao.edu.co:10614/15895 |
| network_acronym_str |
REPOUAO2 |
| network_name_str |
RED: Repositorio Educativo Digital UAO |
| repository_id_str |
|
| dc.title.eng.fl_str_mv |
Exploring the safety of pllans-ii and antitumoral potential of its recombinant isoform in cervical cancer therapy |
| title |
Exploring the safety of pllans-ii and antitumoral potential of its recombinant isoform in cervical cancer therapy |
| spellingShingle |
Exploring the safety of pllans-ii and antitumoral potential of its recombinant isoform in cervical cancer therapy Bioprospecting Snake venom molecules PLA2 Recombinant production Drug discovery Anticancer agents |
| title_short |
Exploring the safety of pllans-ii and antitumoral potential of its recombinant isoform in cervical cancer therapy |
| title_full |
Exploring the safety of pllans-ii and antitumoral potential of its recombinant isoform in cervical cancer therapy |
| title_fullStr |
Exploring the safety of pllans-ii and antitumoral potential of its recombinant isoform in cervical cancer therapy |
| title_full_unstemmed |
Exploring the safety of pllans-ii and antitumoral potential of its recombinant isoform in cervical cancer therapy |
| title_sort |
Exploring the safety of pllans-ii and antitumoral potential of its recombinant isoform in cervical cancer therapy |
| dc.creator.fl_str_mv |
Sevilla-Sánchez, María José Montoya-Gómez, Alejandro Osorno-Valencia, Daniel Mosquera-Escudero, Mildrey Jiménez-Charris, Eliécer Montealegre Sánchez, Leonel Ives |
| dc.contributor.author.none.fl_str_mv |
Sevilla-Sánchez, María José Montoya-Gómez, Alejandro Osorno-Valencia, Daniel Mosquera-Escudero, Mildrey Jiménez-Charris, Eliécer Montealegre Sánchez, Leonel Ives |
| dc.subject.proposal.eng.fl_str_mv |
Bioprospecting Snake venom molecules PLA2 Recombinant production Drug discovery Anticancer agents |
| topic |
Bioprospecting Snake venom molecules PLA2 Recombinant production Drug discovery Anticancer agents |
| description |
he antitumor potential of proteins from snake venoms has been studied in recent decades, and evidence has emerged that phospholipases A2 can selectively attack cells of various types of tumors. Previous results have shown that phospholipase A2 “Pllans-II,” isolated from Porthidium lansbergii lansbergii snake venom, displayed antitumoral activity on cervical cancer and did not alter the viability of non-tumorigenic cells. However, until now, there was no evidence of its safety at the local and systemic levels, nor had experiments been developed to demonstrate that its production using recombinant technology allows us to obtain a molecule with effects similar to those generated by native phospholipase. Thus, we evaluated the impact caused by Pllans-II on murine biomodels, determining whether it induced local hemorrhage or increased pro-inflammatory and liver damage markers and histological alterations in the liver and kidneys. Additionally, the protein was produced using recombinant technology using a pET28a expression vector and the BL21 (DE3) Escherichia coli strain. Equally, its enzymatic activity and anticancer effect were evaluated on cervical cancer lines such as HeLa and Ca Ski. The results demonstrated that Pllans-II did not generate hemorrhagic activity, nor did it increase the pro-inflammatory cytokines IL-6, IL-1B, or TNF-α at doses of 3.28, 1.64, and 0.82 mg/kg. There was also no evidence of organ damage, and only ALT and AST increased in mild levels at the two highest concentrations. Additionally, the recombinant version of Pllans-II showed conservation in its catalytic activity and the ability to generate death in HeLa and Ca Ski cells (42% and 23%, respectively). These results demonstrate the innocuity of Pllans-II at the lowest dose and constitute an advance in considering a molecule produced using recombinant technology a drug candidate for selective attacks against cervical cancer |
| publishDate |
2023 |
| dc.date.issued.none.fl_str_mv |
2023 |
| dc.date.accessioned.none.fl_str_mv |
2024-11-13T17:23:16Z |
| dc.date.available.none.fl_str_mv |
2024-11-13T17:23:16Z |
| dc.type.spa.fl_str_mv |
Artículo de revista |
| dc.type.coarversion.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.coar.eng.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
| dc.type.content.eng.fl_str_mv |
Text |
| dc.type.driver.eng.fl_str_mv |
info:eu-repo/semantics/article |
| dc.type.redcol.eng.fl_str_mv |
http://purl.org/redcol/resource_type/ART |
| dc.type.version.eng.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| format |
http://purl.org/coar/resource_type/c_2df8fbb1 |
| status_str |
publishedVersion |
| dc.identifier.citation.spa.fl_str_mv |
Sevilla-Sánchez, M. J., e.t. al. , (2023). Exploring the safety of pllans-ii and antitumoral potential of its recombinant isoform in cervical cancer therapy. Cells. 12(24). 14 p. https://doi.org/10.3390/cells12242812 |
| dc.identifier.issn.spa.fl_str_mv |
2073-4409 |
| dc.identifier.uri.none.fl_str_mv |
https://hdl.handle.net/10614/15895 |
| dc.identifier.doi.spa.fl_str_mv |
https://doi.org/10.3390/cells12242812 |
| dc.identifier.eissn.spa.fl_str_mv |
20734409 |
| dc.identifier.instname.spa.fl_str_mv |
Universidad Autónoma de Occidente |
| dc.identifier.reponame.spa.fl_str_mv |
Respositorio Educativo Digital UAO |
| dc.identifier.repourl.none.fl_str_mv |
https://red.uao.edu.co/ |
| identifier_str_mv |
Sevilla-Sánchez, M. J., e.t. al. , (2023). Exploring the safety of pllans-ii and antitumoral potential of its recombinant isoform in cervical cancer therapy. Cells. 12(24). 14 p. https://doi.org/10.3390/cells12242812 2073-4409 20734409 Universidad Autónoma de Occidente Respositorio Educativo Digital UAO |
| url |
https://hdl.handle.net/10614/15895 https://doi.org/10.3390/cells12242812 https://red.uao.edu.co/ |
| dc.language.iso.eng.fl_str_mv |
eng |
| language |
eng |
| dc.relation.citationendpage.spa.fl_str_mv |
24 |
| dc.relation.citationissue.spa.fl_str_mv |
24 |
| dc.relation.citationstartpage.spa.fl_str_mv |
1 |
| dc.relation.citationvolume.spa.fl_str_mv |
12 |
| dc.relation.ispartofjournal.spa.fl_str_mv |
Cells |
| dc.relation.references.none.fl_str_mv |
1. Naughton, M.J.; Weaver, K.E. Physical and mental health among cancer survivors: Considerations for long-term care and quality of life. N. C. Med. J. 2014, 75, 283–286. [CrossRef] 2. Schiliro, C.; Firestein, B.L. Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation. Cells 2021, 10, 1056. [CrossRef] 3. Zur Hausen, H. Papillomaviruses and Cancer: From Basic Studies to Clinical Application. Nat. Rev. Cancer 2002, 2, 342–350. [CrossRef] [PubMed] 4. Zhong, L.; Li, Y.; Xiong, L.;Wang,W.;Wu, M.; Yuan, T.; Yang,W.; Tian, C.; Miao, Z.;Wang, T.; et al. Small molecules in targeted cancer therapy: Advances, challenges, and future perspectives. Signal Transduct. Target Ther. 2021, 6, 201. [CrossRef] 5. Vasan, N.; Baselga, J.; Hyman, D.M. A view on drug resistance in cancer. Nature 2019, 575, 299–309. [CrossRef] [PubMed] 6. Sturdza, A.; Pötter, R.; Fokdal, L.U.; Haie-Meder, C.; Tan, L.T.; Mazeron, R.; Petric, P.; Šegedin, B.; Jurgenliemk-Schulz, I.M.; Nomden, C. Image Guided Brachytherapy in Locally Advanced Cervical Cancer: Improved Pelvic Control and Survival in RetroEMBRACE, a Multicenter Cohort Study. Radiother. Oncol. 2016, 120, 428–433. [CrossRef] [PubMed] 7. Huang, M.; Lu, J.J.; Ding, J. Natural products in cancer therapy: Past, present and future. Nat. Prod. Bioprospect. 2021, 11, 5–13. [CrossRef] [PubMed] 8. Montealegre-Sánchez, L.; Gimenes, S.N.C.; Lopes, D.S.; Teixeira, S.C.; Solano-Redondo, L.; de Melo Rodrigues, V.; Jiménez-Charris, E. Antitumoral Potential of Lansbermin-I, a Novel Disintegrin from Porthidium lansbergii lansbergii Venom on Breast Cancer Cells. Curr. Top. Med. Chem. 2019, 19, 2069–2078. [CrossRef] 9. Montoya-Gómez, A.; Montealegre-Sánchez, L.; García-Perdomo, H.A.; Jiménez-Charris, E. Cervical Cancer and Potential Pharmacological Treatment with Snake Venoms. Mol. Biol. Rep. 2020, 47, 4709–4721. [CrossRef] 10. De Oliveira Guimarães, D.; Lopes, D.S.; Azevedo, F.V.P.V.; Gimenes, S.N.C.; Silva, M.A.; Ache, D.C.; Gomes, M.S.R.; Vecchi, L.; Goulart, L.R.; Yoneyama, K.A.G. In Vitro Antitumor and Antiangiogenic Effects of Bothropoidin, a Metalloproteinase from Bothrops Pauloensis Snake Venom. Int. J. Biol. Macromol. 2017, 97, 770–777. [CrossRef] 11. Silva, M.A.; Lopes, D.S.; Teixeira, S.C.; Gimenes, S.N.C.; Azevedo, F.V.P.V.; Polloni, L.; Borges, B.C.; da Silva, M.S.; Barbosa, M.J.; de Oliveira Junior, R.J. Genotoxic Effects of BnSP-6, a Lys-49 Phospholipase A2 (PLA2) Homologue from Bothrops Pauloensis Snake Venom, on MDA-MB-231 Breast Cancer Cells. Int. J. Biol. Macromol. 2018, 118, 311–319. [CrossRef] 12. De Vasconcelos Azevedo, F.V.P.; Zóia, M.A.P.; Lopes, D.S.; Gimenes, S.N.; Vecchi, L.; Alves, P.T.; Rodrigues, R.S.; Silva, A.C.A.; Yoneyama, K.A.G.; Goulart, L.R. Antitumor and Antimetastatic Effects of PLA2-BthTX-II from Bothrops Jararacussu Venom on Human Breast Cancer Cells. Int. J. Biol. Macromol. 2019, 135, 261–273. [CrossRef] [PubMed] 13. Jiménez–Charris, E.; Lopes, D.S.; Gimenes, S.N.C.; Teixeira, S.C.; Montealegre–Sánchez, L.; Solano–Redondo, L.; Fierro–Pérez, L.; de Melo Rodrigues Ávila, V. Antitumor Potential of Pllans–II, an Acidic Asp49–PLA2 from Porthidium Lansbergii Lansbergii Snake Venom on Human Cervical Carcinoma HeLa Cells. Int. J. Biol. Macromol. 2019, 122, 1053–1061. [CrossRef] [PubMed] 14. Montoya-Gómez, A.; Franco, N.R.; Montealegre-Sanchez, L.I.; Solano-Redondo, L.M.; Castillo, A.; Mosquera-Escudero, M.; Jiménez-Charris, E. Pllans–II Induces Cell Death in Cervical Cancer Squamous Epithelial Cells via Unfolded Protein Accumulation and Endoplasmic Reticulum Stress. Molecules 2022, 27, 6491. [CrossRef] 15. Jiménez-Charris, E.; Montealegre-Sanchez, L.; Solano-Redondo, L.; Mora-Obando, D.; Camacho, E.; Castro-Herrera, F.; Fierro-Pérez, L.; Lomonte, B. Proteomic and Functional Analyses of the Venom of Porthidium Lansbergii Lansbergii (Lansberg’s Hognose Viper) from the Atlantic Department of Colombia. J. Proteom. 2015, 114, 287–299. [CrossRef] [PubMed] 16. Jiménez-Charris, E.; Montealegre-Sánchez, L.; Solano-Redondo, L.; Castro-Herrera, F.; Fierro-Pérez, L.; Lomonte, B. Divergent Functional Profiles of Acidic and Basic Phospholipases A2 in the Venom of the Snake Porthidium Lansbergii Lansbergii. Toxicon 2016, 119, 289–298. [CrossRef] 17. Roth, A.; Singer, T. The Application of 3D Cell Models to Support Drug Safety Assessment: Opportunities & Challenges. Adv. Drug Deliv. Rev. 2014, 69, 179–189. [CrossRef] 18. Astashkina, A.; Mann, B.; Grainger, D.W. A Critical Evaluation of in Vitro Cell Culture Models for High-Throughput Drug Screening and Toxicity. Pharmacol. Ther. 2012, 134, 82–106. [CrossRef] 19. Hou, S.; Hsia, C.; Velusamy, M.; Jayakumar, T.; Hsia, C.; Chang, C.; Lin, K.; Lu, Y. Ruthenium Complex, TQ-5, Protects against LPS-induced Macrophage Inflammation and Acute Liver Injury in Mice via Downregulating NF- B Pathways. Int. J. Mol. Med. 2019, 44, 335–345. [CrossRef] 20. Salazar, E.; Salazar, A.M.; Taylor, P.; Ibarra, C.; Rodríguez-Acosta, A.; Sánchez, E.; Pérez, K.; Brito, B.; Guerrero, B. Pro- Inflammatory Response and Hemostatic Disorder Induced by Venom of the Coral Snake Micrurus Tener Tener IN C57BL/6 Mice. Toxicon 2018, 150, 212–219. [CrossRef] 21. Khalil, A.M.; Wahsha, M.A.; Khadra, K.M.A.; Khalaf, M.A.; Al-Najjar, T.H. Biochemical and Histopathological Effects of the Stonefish (Synanceia Verrucosa) Venom in Rats. Toxicon 2018, 142, 45–51. [CrossRef] [PubMed] 22. Schoell, A.R.; Heyde, B.R.; Weir, D.E.; Chiang, P.-C.; Hu, Y.; Tung, D.K. Euthanasia Method for Mice in Rapid Time-Course Pulmonary Pharmacokinetic Studies. J. Am. Assoc. Lab. Anim. Sci. 2009, 48, 506–511. [PubMed] 23. Jenkins, T.P.; Sánchez, A.; Segura, Á.; Vargas, M.; Herrera, M.; Stewart, T.K.; León, G.; Gutiérrez, J.M. An Improved Technique for the Assessment of Venom-Induced Haemorrhage in a Murine Model. Toxicon 2017, 139, 87–93. [CrossRef] [PubMed] 24. De arco-Rodríguez, B.; Montealegre-Sánchez, L.; Solano-Redondo, L.; Castro-Herrera, F.; Ortega, J.G.; Castillo, A.; Vargas-Zapata, C.; Jiménez-Charris, E. Phylogeny and Toxicological Assessments of Two Porthidium lansbergii lansbergii Morphotypes from the Caribbean Region of Colombia. Toxicon 2019, 166, 56–65. [CrossRef] [PubMed] 25. Di Veroli, G.Y.; Fornari, C.; Goldlust, I.; Mills, G.; Koh, S.B.; Bramhall, J.L.; Richards, F.M.; Jodrell, D.I. An Automated Fitting Procedure and Software for Dose-Response Curves with Multiphasic Features. Sci. Rep. 2015, 5, 14701. [CrossRef] [PubMed] 26. Calderon, L.A.; Sobrinho, J.C.; Zaqueo, K.D.; de Moura, A.A.; Grabner, A.N.; Mazzi, M.V.; Marcussi, S.; Nomizo, A.; Fernandes, C.F.C.; Zuliani, J.P.; et al. Antitumoral activity of snake venom proteins: New trends in cancer therapy. Biomed Res. Int. 2014, 2014, 203639. [CrossRef] [PubMed] 27. Chisari, A.; Spinedi, E.; Voirol, M.J.; Giovambattista, A.; Gaillard, R.C. A phospholipase A2-related snake venom (from Crotalus durissus terrificus) stimulates neuroendocrine and immune functions: Determination of different sites of action. Endocrinology 1998, 139, 617–625. [CrossRef] 28. Cedro, R.C.; Menaldo, D.L.; Costa, T.R.; Zoccal, K.F.; Sartim, M.A.; Santos-Filho, N.A.; Faccioli, L.H.; Sampaio, S.V. Cytotoxic and inflammatory potential of a phospholipase A2 from Bothrops jararaca snake venom. J. Venom. Anim. Toxins Incl. Trop. Dis. 2018, 24, 1–14. [CrossRef] 29. Fontana, B.C.; Soares, A.M.; Zuliani, J.P.; Gonçalves, G.M. Role of Toll-like receptors in local effects in a model of experimental envenoming induced by Bothrops jararacussu snake venom and by two phospholipases A2. Toxicon 2022, 214, 145–154. [CrossRef] 30. Marinho, A.D.; de Moraes Silveira, J.A.; Chaves Filho, A.J.M.; Jorge, A.R.C.; Júnior, F.A.N.; Pereira, V.B.M.; de Aquino, P.E.A.; Souza Pereira, C.A.; Evangelista, J.S.A.M.; Macedo, D.S.; et al. Bothrops pauloensis snake venom-derived Asp-49 and Lys-49 phospholipases A2 mediates acute kidney injury by oxidative stress and release of inflammatory cytokines. Toxicon 2021, 190, 31–38. [CrossRef] 31. Zuliani, J.P.; Fernandes, C.M.; Zamuner, S.R.; Gutiérrez, J.M.; Teixeira, C.F.P. Inflammatory Events Induced by Lys-49 and Asp-49 Phospholipases A2 Isolated from Bothrops Asper Snake Venom: Role of Catalytic Activity. Toxicon 2005, 45, 335–346. [CrossRef] 32. Lomonte, B.; Tarkowski, A.; Hanson, L.Å. Host Response to Bothrops Asper Snake Venom: Analysis of Edema Formation, Inflammatory Cells, and Cytokine Release in a Mouse Model. Inflammation 1993, 17, 93–105. [CrossRef] [PubMed] 33. Wei, J.-F.; Li, T.; Wei, X.-L.; Sun, Q.-Y.; Yang, F.-M.; Chen, Q.-Y.; Wang, W.-Y.; Xiong, Y.-L.; He, S.-H. Purification, Characterization and Cytokine Release Function of a Novel Arg-49 Phospholipase A2 from the Venom of Protobothrops Mucrosquamatus. Biochimie 2006, 88, 1331–1342. [CrossRef] [PubMed] 34. Rodríguez, D.R.; Carazo, L.P.; Klímová, K. Interpretación Diagnóstica y Pronóstica de Las Pruebas de Función Hepática. Med. Form. Médica Contin. Acreditado 2012, 11, 733–739. [CrossRef] 35. Busto Bea, V.; Herrero Quirós, C. Pruebas de Función Hepática: B, AST, ALT, FA y GGT. Rev. Española Enfermedades Dig. 2015, 107, 648. 36. Romero-García, J.G.; Mayon Flores, B.A. Evaluación de La Química Hepática Alterada. REMUS Rev. Estud. Med. Univ. Son. 2022, 7, 43–46. [CrossRef] 37. Bordon, K.D.C.F.; Cologna, C.T.; Fornari-Baldo, E.C.; Pinheiro-Júnior, E.L.; Cerni, F.A.; Amorim, F.G.; Pino Anjolette, F.A.; Almeida Cordeiro, F.; Adriano Wiezel, G.; Cardoso, I.A.; et al. From animal poisons and venoms to medicines: Achievements, challenges and perspectives in drug discovery. Front. Pharmacol. 2020, 11, 1132. [CrossRef] [PubMed] 38. Gutiérrez, J.; Lomonte, B. Phospholipase A2 Myotoxins from Bothrops Snake Venoms. Toxicon 1995, 33, 1405–1424. [CrossRef] 39. Howes, J.-M.; Theakston, R.D.G.; Laing, G.D. Neutralization of the Haemorrhagic Activities of Viperine Snake Venoms and Venom Metalloproteinases Using Synthetic Peptide Inhibitors and Chelators. Toxicon 2007, 49, 734–739. [CrossRef] 40. Mukherjee, A.K.; Maity, C.R. The Composition of Naja Naja Venom Samples from Three Districts ofWest Bengal, India. Comp. Biochem. Physiol. Part A Mol. Integr. Physiol. 1998, 119, 621–627. [CrossRef] 41. Teixeira, C.F.P.; Landucci, E.C.T.; Antunes, E.; Chacur, M.; Cury, Y. Inflammatory Effects of Snake Venom Myotoxic Phospholipases A2. Toxicon 2003, 42, 947–962. [CrossRef] [PubMed] 42. Lomonte, B. Lys49 Myotoxins, Secreted Phospholipase A2-like Proteins of Viperid Venoms: A Comprehensive Review. Toxicon 2023, 224, 107024. [CrossRef] [PubMed] 43. Fuly, A.L.; Calil-Elias, S.; Martinez, A.M.B.; Melo, P.A.; Guimarães, J.A. Myotoxicity Induced by an Acidic Asp-49 Phospholipase A2 Isolated from Lachesis Muta Snake Venom: Comparison with Lysophosphatidylcholine. Int. J. Biochem. Cell Biol. 2003, 35, 1470–1481. [CrossRef] [PubMed] 44. Menaldo, D.L.; Jacob-Ferreira, A.L.; Bernardes, C.P.; Cintra, A.C.O.; Sampaio, S.V. Purification Procedure for the Isolation of a PI Metalloprotease and an Acidic Phospholipase A2 From Bothrops Atrox Snake Venom. J. Venom. Anim. Toxins Incl. Trop. Dis. 2015, 21, 1–14. [CrossRef] [PubMed] 45. Hodgson, D.; Gasparini, S.; Drevet, P.; Ducancel, F.; Bouet, F.; Boulain, J.; Harris, J.B.; Menez, A. Production of Recombinant Notechis 110 2L, an Enzymatically Active Mutant of a Phospholipase A2 from Notechis scutatus scutatus Venom, as Directly Generated by Cleavage of a Fusion Protein Produced in Escherichia Coli. Eur. J. Biochem. 1993, 212, 441–446. [CrossRef] [PubMed] 46. Giuliani, C.D.; Iemma, M.R.C.; Bondioli, A.C.V.; Souza, D.H.F.; Ferreira, L.L.; Amaral, A.C.; Salvini, T.F.; Selistre-de-Araujo, H.S. Expression of an Active Recombinant Lysine 49 Phospholipase A2 Myotoxin as a Fusion Protein in Bacteria. Toxicon 2001, 39, 1595–1600. [CrossRef] [PubMed] 47. Takemori, D.; Yoshino, K.; Eba, C.; Nakano, H.; Iwasaki, Y. Extracellular Production of Phospholipase A2 from Streptomyces Violaceoruber by Recombinant Escherichia Coli. Protein Expr. Purif. 2012, 81, 145–150. [CrossRef] [PubMed] 48. Lee, H.-J.; Cho, A.; Hwang, Y.; Park, J.-B.; Kim, S.-K. Engineering of a Microbial Cell Factory for the Extracellular Production of Catalytically Active Phospholipase A2 of Streptomyces Violaceoruber. J. Microbiol. Biotechnol. 2020, 30, 1244. [CrossRef] 49. Russo, R.R.; dos Santos Júnior, N.N.; Cintra, A.C.O.; Figueiredo, L.T.M.; Sampaio, S.V.; Aquino, V.H. Expression, Purification and Virucidal Activity of Two Recombinant Isoforms of Phospholipase A2 from Crotalus durissus terrificus Venom. Arch. Virol. 2019, 164, 1159–1171. [CrossRef] 50. Landeta, C.; Boyd, D.; Beckwith, J. Disulfide Bond Formation in Prokaryotes. Nat. Microbiol. 2018, 3, 270–280. [CrossRef] 51. Karyolaimos, A.; Dolata, K.M.; Antelo-Varela, M.; Mestre Borras, A.; Elfageih, R.; Sievers, S.; Becher, D.; Riedel, K.; de Gier, J.-W. Escherichia Coli Can Adapt Its Protein Translocation Machinery for Enhanced Periplasmic Recombinant Protein Production. Front. Bioeng. Biotechnol. 2020, 7, 465. [CrossRef] 52. Costa, T.R.; Menaldo, D.L.; Oliveira, C.Z.; Santos-Filho, N.A.; Teixeira, S.S.; Nomizo, A.; Fuly, A.L.; Monteiro, M.C.; de Souza, B.M.; Palma, M.S. Myotoxic Phospholipases A2 Isolated from Bothrops Brazili Snake Venom and Synthetic Peptides Derived from Their C-Terminal Region: Cytotoxic Effect on Microorganism and Tumor Cells. Peptides 2008, 29, 1645–1656. [CrossRef] 53. Gebrim, L.C.; Marcussi, S.; Menaldo, D.L.; de Menezes, C.S.R.; Nomizo, A.; Hamaguchi, A.; Silveira-Lacerda, E.P.; Homsi- Brandeburgo, M.I.; Sampaio, S.V.; Soares, A.M. Antitumor Effects of Snake Venom Chemically Modified Lys49 Phospholipase A2-like BthTX-I and a Synthetic Peptide Derived from Its C-Terminal Region. Biologicals 2009, 37, 222–229. [CrossRef] 54. Lomonte, B.; Angulo, Y.; Moreno, E. Synthetic Peptides Derived from the C-Terminal Region of Lys49 Phospholipase A2 Homologues from Viperidae Snake Venoms: Biomimetic Activities and Potential Applications. Curr. Pharm. Des. 2010, 16, 3224–3230. [CrossRef] |
| dc.rights.spa.fl_str_mv |
Derechos reservados - MDPI, 2023 |
| dc.rights.coar.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
| dc.rights.uri.eng.fl_str_mv |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| dc.rights.accessrights.eng.fl_str_mv |
info:eu-repo/semantics/openAccess |
| dc.rights.creativecommons.spa.fl_str_mv |
Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0) |
| rights_invalid_str_mv |
Derechos reservados - MDPI, 2023 https://creativecommons.org/licenses/by-nc-nd/4.0/ Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0) http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.extent.spa.fl_str_mv |
14 páginas |
| dc.format.mimetype.none.fl_str_mv |
application/pdf |
| dc.publisher.eng.fl_str_mv |
MDPI |
| dc.publisher.place.eng.fl_str_mv |
Basel, Switzerland |
| institution |
Universidad Autónoma de Occidente |
| bitstream.url.fl_str_mv |
https://red.uao.edu.co/bitstreams/401ca8df-7f2f-4f44-baf4-7b9de75dcce4/download https://red.uao.edu.co/bitstreams/b874f52d-bd63-47a1-b2bf-0e9e1b7a2e60/download https://red.uao.edu.co/bitstreams/48821635-20f3-4299-a18a-fca65e32fcd1/download https://red.uao.edu.co/bitstreams/b886f2e0-399e-4de6-b80c-b43da501333d/download |
| bitstream.checksum.fl_str_mv |
efa1aec4f5407235577886faf5159ffd 6987b791264a2b5525252450f99b10d1 a7b42eb568c60de8ed38b1a47943d6b2 2a705ac474ce21ce1e83080431b4a76b |
| bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 |
| repository.name.fl_str_mv |
Repositorio Digital Universidad Autonoma de Occidente |
| repository.mail.fl_str_mv |
repositorio@uao.edu.co |
| _version_ |
1834110992200499200 |
| spelling |
Sevilla-Sánchez, María JoséMontoya-Gómez, AlejandroOsorno-Valencia, DanielMosquera-Escudero, MildreyJiménez-Charris, EliécerMontealegre Sánchez, Leonel Ivesvirtual::5775-12024-11-13T17:23:16Z2024-11-13T17:23:16Z2023Sevilla-Sánchez, M. J., e.t. al. , (2023). Exploring the safety of pllans-ii and antitumoral potential of its recombinant isoform in cervical cancer therapy. Cells. 12(24). 14 p. https://doi.org/10.3390/cells122428122073-4409https://hdl.handle.net/10614/15895https://doi.org/10.3390/cells1224281220734409Universidad Autónoma de OccidenteRespositorio Educativo Digital UAOhttps://red.uao.edu.co/he antitumor potential of proteins from snake venoms has been studied in recent decades, and evidence has emerged that phospholipases A2 can selectively attack cells of various types of tumors. Previous results have shown that phospholipase A2 “Pllans-II,” isolated from Porthidium lansbergii lansbergii snake venom, displayed antitumoral activity on cervical cancer and did not alter the viability of non-tumorigenic cells. However, until now, there was no evidence of its safety at the local and systemic levels, nor had experiments been developed to demonstrate that its production using recombinant technology allows us to obtain a molecule with effects similar to those generated by native phospholipase. Thus, we evaluated the impact caused by Pllans-II on murine biomodels, determining whether it induced local hemorrhage or increased pro-inflammatory and liver damage markers and histological alterations in the liver and kidneys. Additionally, the protein was produced using recombinant technology using a pET28a expression vector and the BL21 (DE3) Escherichia coli strain. Equally, its enzymatic activity and anticancer effect were evaluated on cervical cancer lines such as HeLa and Ca Ski. The results demonstrated that Pllans-II did not generate hemorrhagic activity, nor did it increase the pro-inflammatory cytokines IL-6, IL-1B, or TNF-α at doses of 3.28, 1.64, and 0.82 mg/kg. There was also no evidence of organ damage, and only ALT and AST increased in mild levels at the two highest concentrations. Additionally, the recombinant version of Pllans-II showed conservation in its catalytic activity and the ability to generate death in HeLa and Ca Ski cells (42% and 23%, respectively). These results demonstrate the innocuity of Pllans-II at the lowest dose and constitute an advance in considering a molecule produced using recombinant technology a drug candidate for selective attacks against cervical cancer14 páginasapplication/pdfengMDPIBasel, SwitzerlandDerechos reservados - MDPI, 2023https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessAtribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)http://purl.org/coar/access_right/c_abf2Exploring the safety of pllans-ii and antitumoral potential of its recombinant isoform in cervical cancer therapyArtículo de revistahttp://purl.org/coar/resource_type/c_2df8fbb1Textinfo:eu-repo/semantics/articlehttp://purl.org/redcol/resource_type/ARTinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/version/c_970fb48d4fbd8a852424112Cells1. Naughton, M.J.; Weaver, K.E. Physical and mental health among cancer survivors: Considerations for long-term care and quality of life. N. C. Med. J. 2014, 75, 283–286. [CrossRef]2. Schiliro, C.; Firestein, B.L. Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation. Cells 2021, 10, 1056. [CrossRef]3. Zur Hausen, H. Papillomaviruses and Cancer: From Basic Studies to Clinical Application. Nat. Rev. Cancer 2002, 2, 342–350. [CrossRef] [PubMed]4. Zhong, L.; Li, Y.; Xiong, L.;Wang,W.;Wu, M.; Yuan, T.; Yang,W.; Tian, C.; Miao, Z.;Wang, T.; et al. Small molecules in targeted cancer therapy: Advances, challenges, and future perspectives. Signal Transduct. Target Ther. 2021, 6, 201. [CrossRef]5. Vasan, N.; Baselga, J.; Hyman, D.M. A view on drug resistance in cancer. Nature 2019, 575, 299–309. [CrossRef] [PubMed]6. Sturdza, A.; Pötter, R.; Fokdal, L.U.; Haie-Meder, C.; Tan, L.T.; Mazeron, R.; Petric, P.; Šegedin, B.; Jurgenliemk-Schulz, I.M.; Nomden, C. Image Guided Brachytherapy in Locally Advanced Cervical Cancer: Improved Pelvic Control and Survival in RetroEMBRACE, a Multicenter Cohort Study. Radiother. Oncol. 2016, 120, 428–433. [CrossRef] [PubMed]7. Huang, M.; Lu, J.J.; Ding, J. Natural products in cancer therapy: Past, present and future. Nat. Prod. Bioprospect. 2021, 11, 5–13. [CrossRef] [PubMed]8. Montealegre-Sánchez, L.; Gimenes, S.N.C.; Lopes, D.S.; Teixeira, S.C.; Solano-Redondo, L.; de Melo Rodrigues, V.; Jiménez-Charris, E. Antitumoral Potential of Lansbermin-I, a Novel Disintegrin from Porthidium lansbergii lansbergii Venom on Breast Cancer Cells. Curr. Top. Med. Chem. 2019, 19, 2069–2078. [CrossRef]9. Montoya-Gómez, A.; Montealegre-Sánchez, L.; García-Perdomo, H.A.; Jiménez-Charris, E. Cervical Cancer and Potential Pharmacological Treatment with Snake Venoms. Mol. Biol. Rep. 2020, 47, 4709–4721. [CrossRef]10. De Oliveira Guimarães, D.; Lopes, D.S.; Azevedo, F.V.P.V.; Gimenes, S.N.C.; Silva, M.A.; Ache, D.C.; Gomes, M.S.R.; Vecchi, L.; Goulart, L.R.; Yoneyama, K.A.G. In Vitro Antitumor and Antiangiogenic Effects of Bothropoidin, a Metalloproteinase from Bothrops Pauloensis Snake Venom. Int. J. Biol. Macromol. 2017, 97, 770–777. [CrossRef]11. Silva, M.A.; Lopes, D.S.; Teixeira, S.C.; Gimenes, S.N.C.; Azevedo, F.V.P.V.; Polloni, L.; Borges, B.C.; da Silva, M.S.; Barbosa, M.J.; de Oliveira Junior, R.J. Genotoxic Effects of BnSP-6, a Lys-49 Phospholipase A2 (PLA2) Homologue from Bothrops Pauloensis Snake Venom, on MDA-MB-231 Breast Cancer Cells. Int. J. Biol. Macromol. 2018, 118, 311–319. [CrossRef]12. De Vasconcelos Azevedo, F.V.P.; Zóia, M.A.P.; Lopes, D.S.; Gimenes, S.N.; Vecchi, L.; Alves, P.T.; Rodrigues, R.S.; Silva, A.C.A.; Yoneyama, K.A.G.; Goulart, L.R. Antitumor and Antimetastatic Effects of PLA2-BthTX-II from Bothrops Jararacussu Venom on Human Breast Cancer Cells. Int. J. Biol. Macromol. 2019, 135, 261–273. [CrossRef] [PubMed]13. Jiménez–Charris, E.; Lopes, D.S.; Gimenes, S.N.C.; Teixeira, S.C.; Montealegre–Sánchez, L.; Solano–Redondo, L.; Fierro–Pérez, L.; de Melo Rodrigues Ávila, V. Antitumor Potential of Pllans–II, an Acidic Asp49–PLA2 from Porthidium Lansbergii Lansbergii Snake Venom on Human Cervical Carcinoma HeLa Cells. Int. J. Biol. Macromol. 2019, 122, 1053–1061. [CrossRef] [PubMed]14. Montoya-Gómez, A.; Franco, N.R.; Montealegre-Sanchez, L.I.; Solano-Redondo, L.M.; Castillo, A.; Mosquera-Escudero, M.; Jiménez-Charris, E. Pllans–II Induces Cell Death in Cervical Cancer Squamous Epithelial Cells via Unfolded Protein Accumulation and Endoplasmic Reticulum Stress. Molecules 2022, 27, 6491. [CrossRef]15. Jiménez-Charris, E.; Montealegre-Sanchez, L.; Solano-Redondo, L.; Mora-Obando, D.; Camacho, E.; Castro-Herrera, F.; Fierro-Pérez, L.; Lomonte, B. Proteomic and Functional Analyses of the Venom of Porthidium Lansbergii Lansbergii (Lansberg’s Hognose Viper) from the Atlantic Department of Colombia. J. Proteom. 2015, 114, 287–299. [CrossRef] [PubMed]16. Jiménez-Charris, E.; Montealegre-Sánchez, L.; Solano-Redondo, L.; Castro-Herrera, F.; Fierro-Pérez, L.; Lomonte, B. Divergent Functional Profiles of Acidic and Basic Phospholipases A2 in the Venom of the Snake Porthidium Lansbergii Lansbergii. Toxicon 2016, 119, 289–298. [CrossRef]17. Roth, A.; Singer, T. The Application of 3D Cell Models to Support Drug Safety Assessment: Opportunities & Challenges. Adv. Drug Deliv. Rev. 2014, 69, 179–189. [CrossRef]18. Astashkina, A.; Mann, B.; Grainger, D.W. A Critical Evaluation of in Vitro Cell Culture Models for High-Throughput Drug Screening and Toxicity. Pharmacol. Ther. 2012, 134, 82–106. [CrossRef]19. Hou, S.; Hsia, C.; Velusamy, M.; Jayakumar, T.; Hsia, C.; Chang, C.; Lin, K.; Lu, Y. Ruthenium Complex, TQ-5, Protects against LPS-induced Macrophage Inflammation and Acute Liver Injury in Mice via Downregulating NF- B Pathways. Int. J. Mol. Med. 2019, 44, 335–345. [CrossRef]20. Salazar, E.; Salazar, A.M.; Taylor, P.; Ibarra, C.; Rodríguez-Acosta, A.; Sánchez, E.; Pérez, K.; Brito, B.; Guerrero, B. Pro- Inflammatory Response and Hemostatic Disorder Induced by Venom of the Coral Snake Micrurus Tener Tener IN C57BL/6 Mice. Toxicon 2018, 150, 212–219. [CrossRef]21. Khalil, A.M.; Wahsha, M.A.; Khadra, K.M.A.; Khalaf, M.A.; Al-Najjar, T.H. Biochemical and Histopathological Effects of the Stonefish (Synanceia Verrucosa) Venom in Rats. Toxicon 2018, 142, 45–51. [CrossRef] [PubMed]22. Schoell, A.R.; Heyde, B.R.; Weir, D.E.; Chiang, P.-C.; Hu, Y.; Tung, D.K. Euthanasia Method for Mice in Rapid Time-Course Pulmonary Pharmacokinetic Studies. J. Am. Assoc. Lab. Anim. Sci. 2009, 48, 506–511. [PubMed]23. Jenkins, T.P.; Sánchez, A.; Segura, Á.; Vargas, M.; Herrera, M.; Stewart, T.K.; León, G.; Gutiérrez, J.M. An Improved Technique for the Assessment of Venom-Induced Haemorrhage in a Murine Model. Toxicon 2017, 139, 87–93. [CrossRef] [PubMed]24. De arco-Rodríguez, B.; Montealegre-Sánchez, L.; Solano-Redondo, L.; Castro-Herrera, F.; Ortega, J.G.; Castillo, A.; Vargas-Zapata, C.; Jiménez-Charris, E. Phylogeny and Toxicological Assessments of Two Porthidium lansbergii lansbergii Morphotypes from the Caribbean Region of Colombia. Toxicon 2019, 166, 56–65. [CrossRef] [PubMed]25. Di Veroli, G.Y.; Fornari, C.; Goldlust, I.; Mills, G.; Koh, S.B.; Bramhall, J.L.; Richards, F.M.; Jodrell, D.I. An Automated Fitting Procedure and Software for Dose-Response Curves with Multiphasic Features. Sci. Rep. 2015, 5, 14701. [CrossRef] [PubMed]26. Calderon, L.A.; Sobrinho, J.C.; Zaqueo, K.D.; de Moura, A.A.; Grabner, A.N.; Mazzi, M.V.; Marcussi, S.; Nomizo, A.; Fernandes, C.F.C.; Zuliani, J.P.; et al. Antitumoral activity of snake venom proteins: New trends in cancer therapy. Biomed Res. Int. 2014, 2014, 203639. [CrossRef] [PubMed]27. Chisari, A.; Spinedi, E.; Voirol, M.J.; Giovambattista, A.; Gaillard, R.C. A phospholipase A2-related snake venom (from Crotalus durissus terrificus) stimulates neuroendocrine and immune functions: Determination of different sites of action. Endocrinology 1998, 139, 617–625. [CrossRef]28. Cedro, R.C.; Menaldo, D.L.; Costa, T.R.; Zoccal, K.F.; Sartim, M.A.; Santos-Filho, N.A.; Faccioli, L.H.; Sampaio, S.V. Cytotoxic and inflammatory potential of a phospholipase A2 from Bothrops jararaca snake venom. J. Venom. Anim. Toxins Incl. Trop. Dis. 2018, 24, 1–14. [CrossRef]29. Fontana, B.C.; Soares, A.M.; Zuliani, J.P.; Gonçalves, G.M. Role of Toll-like receptors in local effects in a model of experimental envenoming induced by Bothrops jararacussu snake venom and by two phospholipases A2. Toxicon 2022, 214, 145–154. [CrossRef]30. Marinho, A.D.; de Moraes Silveira, J.A.; Chaves Filho, A.J.M.; Jorge, A.R.C.; Júnior, F.A.N.; Pereira, V.B.M.; de Aquino, P.E.A.; Souza Pereira, C.A.; Evangelista, J.S.A.M.; Macedo, D.S.; et al. Bothrops pauloensis snake venom-derived Asp-49 and Lys-49 phospholipases A2 mediates acute kidney injury by oxidative stress and release of inflammatory cytokines. Toxicon 2021, 190, 31–38. [CrossRef]31. Zuliani, J.P.; Fernandes, C.M.; Zamuner, S.R.; Gutiérrez, J.M.; Teixeira, C.F.P. Inflammatory Events Induced by Lys-49 and Asp-49 Phospholipases A2 Isolated from Bothrops Asper Snake Venom: Role of Catalytic Activity. Toxicon 2005, 45, 335–346. [CrossRef]32. Lomonte, B.; Tarkowski, A.; Hanson, L.Å. Host Response to Bothrops Asper Snake Venom: Analysis of Edema Formation, Inflammatory Cells, and Cytokine Release in a Mouse Model. Inflammation 1993, 17, 93–105. [CrossRef] [PubMed]33. Wei, J.-F.; Li, T.; Wei, X.-L.; Sun, Q.-Y.; Yang, F.-M.; Chen, Q.-Y.; Wang, W.-Y.; Xiong, Y.-L.; He, S.-H. Purification, Characterization and Cytokine Release Function of a Novel Arg-49 Phospholipase A2 from the Venom of Protobothrops Mucrosquamatus. Biochimie 2006, 88, 1331–1342. [CrossRef] [PubMed]34. Rodríguez, D.R.; Carazo, L.P.; Klímová, K. Interpretación Diagnóstica y Pronóstica de Las Pruebas de Función Hepática. Med. Form. Médica Contin. Acreditado 2012, 11, 733–739. [CrossRef]35. Busto Bea, V.; Herrero Quirós, C. Pruebas de Función Hepática: B, AST, ALT, FA y GGT. Rev. Española Enfermedades Dig. 2015, 107, 648.36. Romero-García, J.G.; Mayon Flores, B.A. Evaluación de La Química Hepática Alterada. REMUS Rev. Estud. Med. Univ. Son. 2022, 7, 43–46. [CrossRef]37. Bordon, K.D.C.F.; Cologna, C.T.; Fornari-Baldo, E.C.; Pinheiro-Júnior, E.L.; Cerni, F.A.; Amorim, F.G.; Pino Anjolette, F.A.; Almeida Cordeiro, F.; Adriano Wiezel, G.; Cardoso, I.A.; et al. From animal poisons and venoms to medicines: Achievements, challenges and perspectives in drug discovery. Front. Pharmacol. 2020, 11, 1132. [CrossRef] [PubMed]38. Gutiérrez, J.; Lomonte, B. Phospholipase A2 Myotoxins from Bothrops Snake Venoms. Toxicon 1995, 33, 1405–1424. [CrossRef]39. Howes, J.-M.; Theakston, R.D.G.; Laing, G.D. Neutralization of the Haemorrhagic Activities of Viperine Snake Venoms and Venom Metalloproteinases Using Synthetic Peptide Inhibitors and Chelators. Toxicon 2007, 49, 734–739. [CrossRef]40. Mukherjee, A.K.; Maity, C.R. The Composition of Naja Naja Venom Samples from Three Districts ofWest Bengal, India. Comp. Biochem. Physiol. Part A Mol. Integr. Physiol. 1998, 119, 621–627. [CrossRef]41. Teixeira, C.F.P.; Landucci, E.C.T.; Antunes, E.; Chacur, M.; Cury, Y. Inflammatory Effects of Snake Venom Myotoxic Phospholipases A2. Toxicon 2003, 42, 947–962. [CrossRef] [PubMed]42. Lomonte, B. Lys49 Myotoxins, Secreted Phospholipase A2-like Proteins of Viperid Venoms: A Comprehensive Review. Toxicon 2023, 224, 107024. [CrossRef] [PubMed]43. Fuly, A.L.; Calil-Elias, S.; Martinez, A.M.B.; Melo, P.A.; Guimarães, J.A. Myotoxicity Induced by an Acidic Asp-49 Phospholipase A2 Isolated from Lachesis Muta Snake Venom: Comparison with Lysophosphatidylcholine. Int. J. Biochem. Cell Biol. 2003, 35, 1470–1481. [CrossRef] [PubMed]44. Menaldo, D.L.; Jacob-Ferreira, A.L.; Bernardes, C.P.; Cintra, A.C.O.; Sampaio, S.V. Purification Procedure for the Isolation of a PI Metalloprotease and an Acidic Phospholipase A2 From Bothrops Atrox Snake Venom. J. Venom. Anim. Toxins Incl. Trop. Dis. 2015, 21, 1–14. [CrossRef] [PubMed]45. Hodgson, D.; Gasparini, S.; Drevet, P.; Ducancel, F.; Bouet, F.; Boulain, J.; Harris, J.B.; Menez, A. Production of Recombinant Notechis 110 2L, an Enzymatically Active Mutant of a Phospholipase A2 from Notechis scutatus scutatus Venom, as Directly Generated by Cleavage of a Fusion Protein Produced in Escherichia Coli. Eur. J. Biochem. 1993, 212, 441–446. [CrossRef] [PubMed]46. Giuliani, C.D.; Iemma, M.R.C.; Bondioli, A.C.V.; Souza, D.H.F.; Ferreira, L.L.; Amaral, A.C.; Salvini, T.F.; Selistre-de-Araujo, H.S. Expression of an Active Recombinant Lysine 49 Phospholipase A2 Myotoxin as a Fusion Protein in Bacteria. Toxicon 2001, 39, 1595–1600. [CrossRef] [PubMed]47. Takemori, D.; Yoshino, K.; Eba, C.; Nakano, H.; Iwasaki, Y. Extracellular Production of Phospholipase A2 from Streptomyces Violaceoruber by Recombinant Escherichia Coli. Protein Expr. Purif. 2012, 81, 145–150. [CrossRef] [PubMed]48. Lee, H.-J.; Cho, A.; Hwang, Y.; Park, J.-B.; Kim, S.-K. Engineering of a Microbial Cell Factory for the Extracellular Production of Catalytically Active Phospholipase A2 of Streptomyces Violaceoruber. J. Microbiol. Biotechnol. 2020, 30, 1244. [CrossRef]49. Russo, R.R.; dos Santos Júnior, N.N.; Cintra, A.C.O.; Figueiredo, L.T.M.; Sampaio, S.V.; Aquino, V.H. Expression, Purification and Virucidal Activity of Two Recombinant Isoforms of Phospholipase A2 from Crotalus durissus terrificus Venom. Arch. Virol. 2019, 164, 1159–1171. [CrossRef]50. Landeta, C.; Boyd, D.; Beckwith, J. Disulfide Bond Formation in Prokaryotes. Nat. Microbiol. 2018, 3, 270–280. [CrossRef]51. Karyolaimos, A.; Dolata, K.M.; Antelo-Varela, M.; Mestre Borras, A.; Elfageih, R.; Sievers, S.; Becher, D.; Riedel, K.; de Gier, J.-W. Escherichia Coli Can Adapt Its Protein Translocation Machinery for Enhanced Periplasmic Recombinant Protein Production. Front. Bioeng. Biotechnol. 2020, 7, 465. [CrossRef]52. Costa, T.R.; Menaldo, D.L.; Oliveira, C.Z.; Santos-Filho, N.A.; Teixeira, S.S.; Nomizo, A.; Fuly, A.L.; Monteiro, M.C.; de Souza, B.M.; Palma, M.S. Myotoxic Phospholipases A2 Isolated from Bothrops Brazili Snake Venom and Synthetic Peptides Derived from Their C-Terminal Region: Cytotoxic Effect on Microorganism and Tumor Cells. Peptides 2008, 29, 1645–1656. [CrossRef]53. Gebrim, L.C.; Marcussi, S.; Menaldo, D.L.; de Menezes, C.S.R.; Nomizo, A.; Hamaguchi, A.; Silveira-Lacerda, E.P.; Homsi- Brandeburgo, M.I.; Sampaio, S.V.; Soares, A.M. Antitumor Effects of Snake Venom Chemically Modified Lys49 Phospholipase A2-like BthTX-I and a Synthetic Peptide Derived from Its C-Terminal Region. Biologicals 2009, 37, 222–229. [CrossRef]54. Lomonte, B.; Angulo, Y.; Moreno, E. Synthetic Peptides Derived from the C-Terminal Region of Lys49 Phospholipase A2 Homologues from Viperidae Snake Venoms: Biomimetic Activities and Potential Applications. Curr. Pharm. Des. 2010, 16, 3224–3230. [CrossRef]BioprospectingSnake venom moleculesPLA2Recombinant productionDrug discoveryAnticancer agentsComunidad generalPublication279d68cb-eefc-4e2e-9671-1418584c99f5virtual::5775-1279d68cb-eefc-4e2e-9671-1418584c99f5virtual::5775-1https://scholar.google.es/citations?user=C1-P7LUAAAAJ&hl=esvirtual::5775-10000-0001-7057-717Xvirtual::5775-1ORIGINALExploring_the_Safety_of_Pllans-II_and_Antitumoral_Potential_of_Its_Recombinant_Isoform_in_Cervical_Cancer_Therapy.pdfExploring_the_Safety_of_Pllans-II_and_Antitumoral_Potential_of_Its_Recombinant_Isoform_in_Cervical_Cancer_Therapy.pdfArchivo texto completo del artículo de revista, PDFapplication/pdf3041009https://red.uao.edu.co/bitstreams/401ca8df-7f2f-4f44-baf4-7b9de75dcce4/downloadefa1aec4f5407235577886faf5159ffdMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81672https://red.uao.edu.co/bitstreams/b874f52d-bd63-47a1-b2bf-0e9e1b7a2e60/download6987b791264a2b5525252450f99b10d1MD52TEXTExploring_the_Safety_of_Pllans-II_and_Antitumoral_Potential_of_Its_Recombinant_Isoform_in_Cervical_Cancer_Therapy.pdf.txtExploring_the_Safety_of_Pllans-II_and_Antitumoral_Potential_of_Its_Recombinant_Isoform_in_Cervical_Cancer_Therapy.pdf.txtExtracted texttext/plain66202https://red.uao.edu.co/bitstreams/48821635-20f3-4299-a18a-fca65e32fcd1/downloada7b42eb568c60de8ed38b1a47943d6b2MD53THUMBNAILExploring_the_Safety_of_Pllans-II_and_Antitumoral_Potential_of_Its_Recombinant_Isoform_in_Cervical_Cancer_Therapy.pdf.jpgExploring_the_Safety_of_Pllans-II_and_Antitumoral_Potential_of_Its_Recombinant_Isoform_in_Cervical_Cancer_Therapy.pdf.jpgGenerated Thumbnailimage/jpeg15620https://red.uao.edu.co/bitstreams/b886f2e0-399e-4de6-b80c-b43da501333d/download2a705ac474ce21ce1e83080431b4a76bMD5410614/15895oai:red.uao.edu.co:10614/158952024-11-16 03:00:24.142https://creativecommons.org/licenses/by-nc-nd/4.0/Derechos reservados - MDPI, 2023open.accesshttps://red.uao.edu.coRepositorio Digital Universidad Autonoma de Occidenterepositorio@uao.edu.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 |