Exploring the Safety of <i>Pllans-II</i> and Antitumoral Potential of Its Recombinant Isoform in Cervical Cancer Therapy
The antitumor potential of proteins from snake venoms has been studied in recent decades, and evidence has emerged that phospholipases A<sub>2</sub> can selectively attack cells of various types of tumors. Previous results have shown that phospholipase A<sub>2</sub> “<i>...
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MDPI AG
2023-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/24/2812 |
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| author | María José Sevilla-Sánchez Alejandro Montoya-Gómez Daniel Osorno-Valencia Leonel Montealegre-Sánchez Mildrey Mosquera-Escudero Eliécer Jiménez-Charris |
| author_facet | María José Sevilla-Sánchez Alejandro Montoya-Gómez Daniel Osorno-Valencia Leonel Montealegre-Sánchez Mildrey Mosquera-Escudero Eliécer Jiménez-Charris |
| author_sort | María José Sevilla-Sánchez |
| collection | DOAJ |
| description | The antitumor potential of proteins from snake venoms has been studied in recent decades, and evidence has emerged that phospholipases A<sub>2</sub> can selectively attack cells of various types of tumors. Previous results have shown that phospholipase A<sub>2</sub> “<i>Pllans-II</i>,<i>”</i> isolated from <i>Porthidium lansbergii lansbergii</i> 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 <i>Pllans-II</i> 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) <i>Escherichia coli</i> strain. Equally, its enzymatic activity and anticancer effect were evaluated on cervical cancer lines such as HeLa and Ca Ski. The results demonstrated that <i>Pllans-II</i> 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 <i>Pllans-II</i> 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 <i>Pllans-II</i> 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. |
| first_indexed | 2024-03-08T20:55:05Z |
| format | Article |
| id | doaj.art-ce42e22343d341fba11f1d084dd3dc41 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-08T20:55:05Z |
| publishDate | 2023-12-01 |
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| series | Cells |
| spelling | doaj.art-ce42e22343d341fba11f1d084dd3dc412023-12-22T13:59:39ZengMDPI AGCells2073-44092023-12-011224281210.3390/cells12242812Exploring the Safety of <i>Pllans-II</i> and Antitumoral Potential of Its Recombinant Isoform in Cervical Cancer TherapyMaría José Sevilla-Sánchez0Alejandro Montoya-Gómez1Daniel Osorno-Valencia2Leonel Montealegre-Sánchez3Mildrey Mosquera-Escudero4Eliécer Jiménez-Charris5Grupo de Nutrición, Facultad de Salud, Universidad del Valle, Cali 760043, ColombiaGrupo de Nutrición, Facultad de Salud, Universidad del Valle, Cali 760043, ColombiaGrupo de Nutrición, Facultad de Salud, Universidad del Valle, Cali 760043, ColombiaGrupo de Nutrición, Facultad de Salud, Universidad del Valle, Cali 760043, ColombiaGrupo de Nutrición, Facultad de Salud, Universidad del Valle, Cali 760043, ColombiaGrupo de Nutrición, Facultad de Salud, Universidad del Valle, Cali 760043, ColombiaThe antitumor potential of proteins from snake venoms has been studied in recent decades, and evidence has emerged that phospholipases A<sub>2</sub> can selectively attack cells of various types of tumors. Previous results have shown that phospholipase A<sub>2</sub> “<i>Pllans-II</i>,<i>”</i> isolated from <i>Porthidium lansbergii lansbergii</i> 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 <i>Pllans-II</i> 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) <i>Escherichia coli</i> strain. Equally, its enzymatic activity and anticancer effect were evaluated on cervical cancer lines such as HeLa and Ca Ski. The results demonstrated that <i>Pllans-II</i> 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 <i>Pllans-II</i> 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 <i>Pllans-II</i> 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.https://www.mdpi.com/2073-4409/12/24/2812bioprospectingsnake venom moleculesPLA<sub>2</sub>recombinant productiondrug discoveryanticancer agents |
| spellingShingle | María José Sevilla-Sánchez Alejandro Montoya-Gómez Daniel Osorno-Valencia Leonel Montealegre-Sánchez Mildrey Mosquera-Escudero Eliécer Jiménez-Charris Exploring the Safety of <i>Pllans-II</i> and Antitumoral Potential of Its Recombinant Isoform in Cervical Cancer Therapy Cells bioprospecting snake venom molecules PLA<sub>2</sub> recombinant production drug discovery anticancer agents |
| title | Exploring the Safety of <i>Pllans-II</i> and Antitumoral Potential of Its Recombinant Isoform in Cervical Cancer Therapy |
| title_full | Exploring the Safety of <i>Pllans-II</i> and Antitumoral Potential of Its Recombinant Isoform in Cervical Cancer Therapy |
| title_fullStr | Exploring the Safety of <i>Pllans-II</i> and Antitumoral Potential of Its Recombinant Isoform in Cervical Cancer Therapy |
| title_full_unstemmed | Exploring the Safety of <i>Pllans-II</i> and Antitumoral Potential of Its Recombinant Isoform in Cervical Cancer Therapy |
| title_short | Exploring the Safety of <i>Pllans-II</i> and Antitumoral Potential of Its Recombinant Isoform in Cervical Cancer Therapy |
| title_sort | exploring the safety of i pllans ii i and antitumoral potential of its recombinant isoform in cervical cancer therapy |
| topic | bioprospecting snake venom molecules PLA<sub>2</sub> recombinant production drug discovery anticancer agents |
| url | https://www.mdpi.com/2073-4409/12/24/2812 |
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