Xc- System as a Possible Target for ConBr Lectin Interaction in Glioma Cells
Vanir Reis Pinto-Junior,
Rodrigo Lopes Seeger,
Cláudio Henrique Dahne Souza-Filho,
Angela Patricia França,
Nicole Sartori,
Messias Vital Oliveira,
Vinicius Jose Silva Osterne,
Kyria Santiago Nascimento,
Rodrigo Bainy Leal,
Benildo Sousa Cavada
Affiliations
Vanir Reis Pinto-Junior
Department of Biochemistry and Molecular Biology, BioMolLab, Federal University of Ceara, Fortaleza 60020-181, CE, Brazil
Rodrigo Lopes Seeger
Department of Biochemistry and Postgraduate Program in Biochemistry, Center for Biological Sciences, University Campus, Federal University of Santa Catarina, Florianópolis 88040-900, SC, Brazil
Cláudio Henrique Dahne Souza-Filho
Department of Biochemistry and Postgraduate Program in Biochemistry, Center for Biological Sciences, University Campus, Federal University of Santa Catarina, Florianópolis 88040-900, SC, Brazil
Angela Patricia França
Department of Biochemistry and Postgraduate Program in Biochemistry, Center for Biological Sciences, University Campus, Federal University of Santa Catarina, Florianópolis 88040-900, SC, Brazil
Nicole Sartori
Department of Biochemistry and Postgraduate Program in Biochemistry, Center for Biological Sciences, University Campus, Federal University of Santa Catarina, Florianópolis 88040-900, SC, Brazil
Messias Vital Oliveira
Department of Biochemistry and Molecular Biology, BioMolLab, Federal University of Ceara, Fortaleza 60020-181, CE, Brazil
Vinicius Jose Silva Osterne
Department of Biochemistry and Molecular Biology, BioMolLab, Federal University of Ceara, Fortaleza 60020-181, CE, Brazil
Kyria Santiago Nascimento
Department of Biochemistry and Molecular Biology, BioMolLab, Federal University of Ceara, Fortaleza 60020-181, CE, Brazil
Rodrigo Bainy Leal
Department of Biochemistry and Postgraduate Program in Biochemistry, Center for Biological Sciences, University Campus, Federal University of Santa Catarina, Florianópolis 88040-900, SC, Brazil
Benildo Sousa Cavada
Department of Biochemistry and Molecular Biology, BioMolLab, Federal University of Ceara, Fortaleza 60020-181, CE, Brazil
Studies have revealed the dependence of glioma cells on iron, making them sensitive to ferroptosis. Ferroptosis can be triggered by inhibition of the xc- system, resulting in redox imbalance and membrane lipid peroxidation. The xc- system is composed of two coupled proteins, xCT and CD98hc. The control of transporters, such as xCT, by the CD98hc glycoprotein suggests that molecules targeting glycans may have an impact on the treatment of glioma. This study evaluated the effect of the Canavalia brasiliensis (ConBr) lectin on C6 glioma cells and compared it with erastin, an xc- system inhibitor. Both induced dose-dependent cell death, accompanied by an increase in the production of reactive oxygen species and a decrease in reduced glutathione. However, co-treatment did not show an additive effect. The analysis was updated by molecular dynamics assessments of the xc- system interacting with ConBr or erastin. The interaction of erastin with the xc- system affects its interaction with ConBr, reducing the antagonistic effect when both are in the protein complex. The data show that ConBr is effective in inducing cell death in glioma cells and regulates the xc system through interaction with CD98hc glycans, showing that lectins have the potential to promote ferroptosis in glioma cells.
