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

Autor: Habib Karoui, Kenneth J. Clemetson, Timothy N. C. Wells, Houcemeddine Othman, Soumaya Souid, José Neptuno Rodríguez-López, Ichrak Riahi-Chebbi, Zohra Aloui, Ammar Gasmi, Edith M. Magnenat, Najet Srairi-Abid, Khadija Essafi-Benkhadir, Manel B Hammouda
Přispěvatelé: Université de Tunis El Manar (UTM), Laboratoire d'Epidémiologie Moléculaire et de Pathologie Expérimentale Appliquée aux Maladies Infectieuses (LR11IPT04), Université de Tunis El Manar (UTM)-Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Universidad de Murcia, Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules (LR11IPT08), Institut Pasteur de Tunis, Serono Pharmaceutical Research Institute [Geneva, Switzerland], Université de Berne, This work was supported by grants from the Tunisian Ministry of Higher Education and Scientific Research (LR11IPT04/LR16IPT04) and the Institut Pasteur de Tunis to Khadija Essafi-Benkhadir (PCI_04_2012) and by the Ministerio de Economia y Competitividad (MINECO, Co-financing with Fondos FEDER) (SAF2016-77241-R) and the Fundación Séneca, the Región de Murcia (FS-RM) (19304/PI/14) to José Neptuno Rodríguez-López. Manel B. Hammouda was supported by a grant of Erasmus mundus EU Mare Nostrum.
Rok vydání: 2018
Předmět:
Models
Molecular
0301 basic medicine
Protein Conformation
Apoptosis
Biochemistry
Cisplatin efficacy
Cell Movement
C-type lectin
Protein Interaction Mapping
Viperidae
Melanoma
RGD motif
Integrin alphaVbeta3
Cell adhesion molecule
Chemistry
Drug Synergism
Neoplasm Proteins
3. Good health
Gene Expression Regulation
Neoplastic
Molecular Docking Simulation
Anti-tumoral effect
medicine.drug
Macrovipecetin
Mechanistic characterization
Biophysics
Antineoplastic Agents
Viper Venoms
03 medical and health sciences
Snaclec
Cell Line
Tumor
Cell Adhesion
medicine
Animals
Humans
Lectins
C-Type
Neoplasm Invasiveness
Protein Interaction Domains and Motifs
Amino Acid Sequence
Viability assay
Cell adhesion
Antineoplastic Agents
Alkylating
Molecular Biology
Protein kinase B
Cisplatin
Sequence Homology
Amino Acid
030104 developmental biology
Drug Resistance
Neoplasm
Cancer research
Drug Screening Assays
Antitumor
Apoptosis Regulatory Proteins
Cell Adhesion Molecules
Sequence Alignment
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Zdroj: Biochimica et Biophysica Acta (BBA)-General Subjects
Biochimica et Biophysica Acta (BBA)-General Subjects, Elsevier, 2018, 1862 (3), pp.600--614. ⟨10.1016/j.bbagen.2017.11.019⟩
ISSN: 0304-4165
DOI: 10.1016/j.bbagen.2017.11.019
Popis: 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.
Databáze: OpenAIRE
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