Lebein, a Snake Venom Disintegrin, Induces Apoptosis in Human Melanoma Cells
Melanoma, the most threatening form of skin cancer, has a very poor prognosis and is characterized by its very invasive and chemoresistant properties. Despite the recent promising news from the field of immunotherapy, there is an urgent need for new therapeutic approaches that are free of resistance...
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MDPI AG
2016-07-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/8/7/206 |
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| author | Manel B. Hammouda María F. Montenegro Luis Sánchez-del-Campo Ons Zakraoui Zohra Aloui Ichrak Riahi-Chebbi Habib Karoui José Neptuno Rodríguez-López Khadija Essafi-Benkhadir |
| author_facet | Manel B. Hammouda María F. Montenegro Luis Sánchez-del-Campo Ons Zakraoui Zohra Aloui Ichrak Riahi-Chebbi Habib Karoui José Neptuno Rodríguez-López Khadija Essafi-Benkhadir |
| author_sort | Manel B. Hammouda |
| collection | DOAJ |
| description | Melanoma, the most threatening form of skin cancer, has a very poor prognosis and is characterized by its very invasive and chemoresistant properties. Despite the recent promising news from the field of immunotherapy, there is an urgent need for new therapeutic approaches that are free of resistance mechanisms and side effects. Anti-neoplasic properties have been highlighted for different disintegrins from snake venom including Lebein; however, the exact effect of Lebein on melanoma has not yet been defined. In this study, we showed that Lebein blocks melanoma cell proliferation and induces a more differentiated phenotype with inhibition of extracellular signal-regulated kinase (ERK) phosphorylation and microphthalmia-associated transcription factor (MITF) overexpression. Melanoma cells became detached but were less invasive with upregulation of E-cadherin after Lebein exposure. Lebein induced a caspase-independent apoptotic program with apoptosis inducing factor (AIF), BCL-2-associated X protein (BAX) and Bim overexpression together with downregulation of B-cell lymphoma-2 (BCL-2). It generated a distinct response in reactive oxygen species (ROS) generation and p53 levels depending on the p53 cell line status (wild type or mutant). Therefore, we propose Lebein as a new candidate for development of potential therapies for melanoma. |
| first_indexed | 2024-04-11T12:11:31Z |
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| language | English |
| last_indexed | 2024-04-11T12:11:31Z |
| publishDate | 2016-07-01 |
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| record_format | Article |
| series | Toxins |
| spelling | doaj.art-3cf95e28d7d44555be6407b0f775fea52022-12-22T04:24:36ZengMDPI AGToxins2072-66512016-07-018720610.3390/toxins8070206toxins8070206Lebein, a Snake Venom Disintegrin, Induces Apoptosis in Human Melanoma CellsManel B. Hammouda0María F. Montenegro1Luis Sánchez-del-Campo2Ons Zakraoui3Zohra Aloui4Ichrak Riahi-Chebbi5Habib Karoui6José Neptuno Rodríguez-López7Khadija Essafi-Benkhadir8Laboratoire d’Epidémiologie Moléculaire et Pathologie Expérimentale Appliquée Aux Maladies Infectieuses (LR11IPT04), Institut Pasteur de Tunis, 1002 Tunis, TunisiaDepartment of Biochemistry and Molecular Biology A, School of Biology, University of Murcia, 30100 Espinardo, Murcia, SpainDepartment of Biochemistry and Molecular Biology A, School of Biology, University of Murcia, 30100 Espinardo, Murcia, SpainLaboratoire d’Epidémiologie Moléculaire et Pathologie Expérimentale Appliquée Aux Maladies Infectieuses (LR11IPT04), Institut Pasteur de Tunis, 1002 Tunis, TunisiaLaboratoire d’Epidémiologie Moléculaire et Pathologie Expérimentale Appliquée Aux Maladies Infectieuses (LR11IPT04), Institut Pasteur de Tunis, 1002 Tunis, TunisiaLaboratoire d’Epidémiologie Moléculaire et Pathologie Expérimentale Appliquée Aux Maladies Infectieuses (LR11IPT04), Institut Pasteur de Tunis, 1002 Tunis, TunisiaLaboratoire d’Epidémiologie Moléculaire et Pathologie Expérimentale Appliquée Aux Maladies Infectieuses (LR11IPT04), Institut Pasteur de Tunis, 1002 Tunis, TunisiaDepartment of Biochemistry and Molecular Biology A, School of Biology, University of Murcia, 30100 Espinardo, Murcia, SpainLaboratoire d’Epidémiologie Moléculaire et Pathologie Expérimentale Appliquée Aux Maladies Infectieuses (LR11IPT04), Institut Pasteur de Tunis, 1002 Tunis, TunisiaMelanoma, the most threatening form of skin cancer, has a very poor prognosis and is characterized by its very invasive and chemoresistant properties. Despite the recent promising news from the field of immunotherapy, there is an urgent need for new therapeutic approaches that are free of resistance mechanisms and side effects. Anti-neoplasic properties have been highlighted for different disintegrins from snake venom including Lebein; however, the exact effect of Lebein on melanoma has not yet been defined. In this study, we showed that Lebein blocks melanoma cell proliferation and induces a more differentiated phenotype with inhibition of extracellular signal-regulated kinase (ERK) phosphorylation and microphthalmia-associated transcription factor (MITF) overexpression. Melanoma cells became detached but were less invasive with upregulation of E-cadherin after Lebein exposure. Lebein induced a caspase-independent apoptotic program with apoptosis inducing factor (AIF), BCL-2-associated X protein (BAX) and Bim overexpression together with downregulation of B-cell lymphoma-2 (BCL-2). It generated a distinct response in reactive oxygen species (ROS) generation and p53 levels depending on the p53 cell line status (wild type or mutant). Therefore, we propose Lebein as a new candidate for development of potential therapies for melanoma.http://www.mdpi.com/2072-6651/8/7/206Lebeindisintegrinsnake venomMacrovipera lebetinamelanomaapoptosis |
| spellingShingle | Manel B. Hammouda María F. Montenegro Luis Sánchez-del-Campo Ons Zakraoui Zohra Aloui Ichrak Riahi-Chebbi Habib Karoui José Neptuno Rodríguez-López Khadija Essafi-Benkhadir Lebein, a Snake Venom Disintegrin, Induces Apoptosis in Human Melanoma Cells Toxins Lebein disintegrin snake venom Macrovipera lebetina melanoma apoptosis |
| title | Lebein, a Snake Venom Disintegrin, Induces Apoptosis in Human Melanoma Cells |
| title_full | Lebein, a Snake Venom Disintegrin, Induces Apoptosis in Human Melanoma Cells |
| title_fullStr | Lebein, a Snake Venom Disintegrin, Induces Apoptosis in Human Melanoma Cells |
| title_full_unstemmed | Lebein, a Snake Venom Disintegrin, Induces Apoptosis in Human Melanoma Cells |
| title_short | Lebein, a Snake Venom Disintegrin, Induces Apoptosis in Human Melanoma Cells |
| title_sort | lebein a snake venom disintegrin induces apoptosis in human melanoma cells |
| topic | Lebein disintegrin snake venom Macrovipera lebetina melanoma apoptosis |
| url | http://www.mdpi.com/2072-6651/8/7/206 |
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