Journal article
Macrovipecetin, a C-type lectin from Macrovipera lebetina venom, inhibits proliferation migration and invasion of SK-MEL-28 human melanoma cells and enhances their sensitivity to cisplatin.
- Hammouda MB Institut Pasteur de Tunis, LR11IPT04/LR16IPT04 Laboratoire d'Epidémiologie Moléculaire et Pathologie Expérimentale Appliquée Aux Maladies Infectieuses, 1002 Tunis, Tunisia; Université de Tunis El Manar, 1068 Tunis, Tunisia; Department of Biochemistry and Molecular Biology A, School of Biology, IMIB, University of Murcia, 30100 Espinardo, Murcia, Spain.
- Riahi-Chebbi I Institut Pasteur de Tunis, LR11IPT04/LR16IPT04 Laboratoire d'Epidémiologie Moléculaire et Pathologie Expérimentale Appliquée Aux Maladies Infectieuses, 1002 Tunis, Tunisia; Université de Tunis El Manar, 1068 Tunis, Tunisia.
- Souid S Institut Pasteur de Tunis, LR11IPT04/LR16IPT04 Laboratoire d'Epidémiologie Moléculaire et Pathologie Expérimentale Appliquée Aux Maladies Infectieuses, 1002 Tunis, Tunisia; Université de Tunis El Manar, 1068 Tunis, Tunisia.
- Othman H Université de Tunis El Manar, 1068 Tunis, Tunisia; Institut Pasteur de Tunis, LR11IPT08 Laboratoire des Venins et Biomolécules thérapeutiques, 1002, Tunisia.
- Aloui Z Institut Pasteur de Tunis, LR11IPT04/LR16IPT04 Laboratoire d'Epidémiologie Moléculaire et Pathologie Expérimentale Appliquée Aux Maladies Infectieuses, 1002 Tunis, Tunisia; Université de Tunis El Manar, 1068 Tunis, Tunisia.
- Srairi-Abid N Université de Tunis El Manar, 1068 Tunis, Tunisia; Institut Pasteur de Tunis, LR11IPT08 Laboratoire des Venins et Biomolécules thérapeutiques, 1002, Tunisia.
- Karoui H Institut Pasteur de Tunis, LR11IPT04/LR16IPT04 Laboratoire d'Epidémiologie Moléculaire et Pathologie Expérimentale Appliquée Aux Maladies Infectieuses, 1002 Tunis, Tunisia; Université de Tunis El Manar, 1068 Tunis, Tunisia.
- Gasmi A Institut Pasteur de Tunis, LR11IPT04/LR16IPT04 Laboratoire d'Epidémiologie Moléculaire et Pathologie Expérimentale Appliquée Aux Maladies Infectieuses, 1002 Tunis, Tunisia; Université de Tunis El Manar, 1068 Tunis, Tunisia.
- Magnenat EM Serono Pharmaceutical Research Institute SA, 14, chemin des Aulx, CH-1228, Plan-les-Ouates, Geneva, Switzerland.
- Wells TNC Serono Pharmaceutical Research Institute SA, 14, chemin des Aulx, CH-1228, Plan-les-Ouates, Geneva, Switzerland.
- Clemetson KJ Department of Clinical Research/Haematology, University of Berne, Inselspital, Murtenstrasse 40, CH-3008 Berne, Switzerland.
- Rodríguez-López JN Department of Biochemistry and Molecular Biology A, School of Biology, IMIB, University of Murcia, 30100 Espinardo, Murcia, Spain. Electronic address: neptuno@um.es.
- Essafi-Benkhadir K Institut Pasteur de Tunis, LR11IPT04/LR16IPT04 Laboratoire d'Epidémiologie Moléculaire et Pathologie Expérimentale Appliquée Aux Maladies Infectieuses, 1002 Tunis, Tunisia; Université de Tunis El Manar, 1068 Tunis, Tunisia. Electronic address: essafi.khadija@pasteur.rns.tn.
- 2017-12-03
Published in:
- Biochimica et biophysica acta. General subjects. - 2018
Anti-tumoral effect
Cisplatin efficacy
Macrovipecetin
Mechanistic characterization
Melanoma
Snaclec
Amino Acid Sequence
Animals
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Apoptosis
Apoptosis Regulatory Proteins
Cell Adhesion
Cell Adhesion Molecules
Cell Line, Tumor
Cell Movement
Cisplatin
Drug Resistance, Neoplasm
Drug Screening Assays, Antitumor
Drug Synergism
Gene Expression Regulation, Neoplastic
Humans
Integrin alphaVbeta3
Lectins, C-Type
Melanoma
Models, Molecular
Molecular Docking Simulation
Neoplasm Invasiveness
Neoplasm Proteins
Protein Conformation
Protein Interaction Domains and Motifs
Protein Interaction Mapping
Sequence Alignment
Sequence Homology, Amino Acid
Viper Venoms
Viperidae
English
BACKGROUND
The resistance of melanoma cells to cisplatin restricts its clinical use. Therefore, the search for novel tumor inhibitors and effective combination treatments that sensitize tumor cells to this drug are still needed. We purified macrovipecetin, a novel heterodimeric C-type lectin, from Macrovipera lebetina snake venom and investigated its anti-tumoral effect on its own or combined with cisplatin, in human melanoma cells.
METHODS
Biochemical characterization, in vitro cells assays such as viability, apoptosis, adhesion, migration, invasion, Western blotting and in silico analysis were used in this study.
RESULTS
Macrovipecetin decreased melanoma cell viability 100 times more than cisplatin. Interestingly, when combined with the drug, macrovipecetin enhanced the sensitivity of SK-MEL-28 cells by augmenting their apoptosis through increased expression of the apoptosis inducing factor (AIF) and activation of ERK1/2, p38, AKT and NF-κB. Moreover, macrovipecetin alone or combined with cisplatin induced the expression of TRADD, p53, Bax, Bim and Bad and down-regulated the Bcl-2 expression and ROS levels in SK-MEL-28 cells. Interestingly, these treatments impaired SK-MEL-28 cell adhesion, migration and invasion through modulating the function and expression of αvβ3 integrin along with regulating E-cadherin, vimentin, β-catenin, c-Src and RhoA expression. In silico study suggested that only the α chain of macrovipecetin interacts with a region overlapping the RGD motif binding site on this integrin.
CONCLUSIONS
We validated the antitumor effect of macrovipecetin when combined, or not, with cisplatin on SK-MEL-28 cells.
GENERAL SIGNIFICANCE
The presented work proposes the potential use of macrovipecetin and cisplatin in combination as an effective anti-melanoma treatment.
The resistance of melanoma cells to cisplatin restricts its clinical use. Therefore, the search for novel tumor inhibitors and effective combination treatments that sensitize tumor cells to this drug are still needed. We purified macrovipecetin, a novel heterodimeric C-type lectin, from Macrovipera lebetina snake venom and investigated its anti-tumoral effect on its own or combined with cisplatin, in human melanoma cells.
METHODS
Biochemical characterization, in vitro cells assays such as viability, apoptosis, adhesion, migration, invasion, Western blotting and in silico analysis were used in this study.
RESULTS
Macrovipecetin decreased melanoma cell viability 100 times more than cisplatin. Interestingly, when combined with the drug, macrovipecetin enhanced the sensitivity of SK-MEL-28 cells by augmenting their apoptosis through increased expression of the apoptosis inducing factor (AIF) and activation of ERK1/2, p38, AKT and NF-κB. Moreover, macrovipecetin alone or combined with cisplatin induced the expression of TRADD, p53, Bax, Bim and Bad and down-regulated the Bcl-2 expression and ROS levels in SK-MEL-28 cells. Interestingly, these treatments impaired SK-MEL-28 cell adhesion, migration and invasion through modulating the function and expression of αvβ3 integrin along with regulating E-cadherin, vimentin, β-catenin, c-Src and RhoA expression. In silico study suggested that only the α chain of macrovipecetin interacts with a region overlapping the RGD motif binding site on this integrin.
CONCLUSIONS
We validated the antitumor effect of macrovipecetin when combined, or not, with cisplatin on SK-MEL-28 cells.
GENERAL SIGNIFICANCE
The presented work proposes the potential use of macrovipecetin and cisplatin in combination as an effective anti-melanoma treatment.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1016/j.bbagen.2017.11.019
- PMID 29196192
- Persistent URL
- https://sonar.ch/global/documents/278667
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