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Lebein, a Snake Venom Disintegrin, Induces Apoptosis in Human Melanoma Cells
Manel B Hammouda1,2,3, María F Montenegro4, Luis Sánchez-Del-Campo5
1Laboratoire d'Epidémiologie Moléculaire et Pathologie Expérimentale Appliquée Aux Maladies Infectieuses (LR11IPT04), Institut Pasteur de Tunis, 1002 Tunis, Tunisia. ma_nel85@hotmail.com.
Abstract:
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.
Insights
Lebein, a snake venom disintegrin, effectively inhibits melanoma cell proliferation and invasiveness. This compound shows potential as a novel therapeutic agent for melanoma, offering a new avenue for cancer treatment.
Area of Science:
- Oncology
- Biochemistry
- Pharmacology
Background:
- Melanoma is an aggressive skin cancer with poor prognosis and resistance to chemotherapy.
- Current treatments, including immunotherapy, necessitate new therapeutic strategies to overcome resistance and side effects.
Purpose of the Study:
- To investigate the anti-neoplastic effects of Lebein, a snake venom disintegrin, on melanoma cells.
- To elucidate the molecular mechanisms underlying Lebein's action in melanoma.
Main Methods:
- Treatment of melanoma cells with Lebein.
- Analysis of cell proliferation, differentiation markers (ERK, MITF, E-cadherin), apoptosis (caspase-independent pathway, AIF, BAX, Bim, BCL-2), and reactive oxygen species (ROS).
- Assessment of p53 levels in wild-type and mutant p53 melanoma cell lines.
Main Results:
- Lebein significantly blocked melanoma cell proliferation and induced a differentiated phenotype.
- Lebein reduced melanoma cell invasiveness by upregulating E-cadherin.
- Lebein triggered caspase-independent apoptosis and modulated ROS and p53 levels differently based on p53 status.
Conclusions:
- Lebein exhibits potent anti-melanoma properties, including inhibition of proliferation and invasiveness.
- Lebein induces melanoma cell differentiation and apoptosis through specific molecular pathways.
- Lebein represents a promising candidate for novel melanoma therapeutic development.
Related Concept Videos
01:31The Intrinsic Apoptotic Pathway
01:17The Extrinsic Apoptotic Pathway