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The lectin DrfL inhibits cell migration, adhesion and triggers autophagy-dependent cell death in glioma cells

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Abstract

Glioblastoma multiforme (GBM) is the most aggressive type of glioma, displaying atypical glycosylation pattern that may modulate signaling pathways involved in tumorigenesis. Lectins are glycan binding proteins with antitumor properties. The present study was designed to evaluate the antitumor capacity of the Dioclea reflexa lectin (DrfL) on glioma cell cultures. Our results demonstrated that DrfL induced morphological changes and cytotoxic effects in glioma cell cultures of C6, U-87MG and GBM1 cell lines. The action of DrfL was dependent upon interaction with glycans, and required a carbohydrate recognition domain (CRD), and the cytotoxic effect was apparently selective for tumor cells, not altering viability and morphology of primary astrocytes. DrfL inhibited tumor cell migration, adhesion, proliferation and survival, and these effects were accompanied by activation of p38MAPK and JNK (p46/54), along with inhibition of Akt and ERK1/2. DrfL also upregulated pro-apoptotic (BNIP3 and PUMA) and autophagic proteins (Atg5 and LC3 cleavage) in GBM cells. Noteworthy, inhibition of autophagy and caspase-8 were both able to attenuate cell death in GBM cells treated with DrfL. Our results indicate that DrfL cytotoxicity against GBM involves modulation of cell pathways, including MAPKs and Akt, which are associated with autophagy and caspase-8 dependent cell death.

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Acknowledgements

This study was supported by the National Council for Scientific and Technological Development (CNPq) Brazil (Projects #309048/2019-2; #439601/2018-5; #CNPq/RENORBIO 407945/2013-0); National Coordination for the Training and Improvement of Higher Education Personnel (CAPES) Brazil via Finance Code 001; Santa Catarina State Research Foundation (FAPESC) Project FAPESC/PRONEX Program—NENASC #1262/2012-9, and FAPESC CP 26/2020 (2021TR000310). AZF, BSC, KSN and RBL are recipients of a Research Scholarship from CNPq (CNPq Research Productivity). We are grateful to the Laboratório Multiusuário de Estudos em Biologia at the Universidade Federal de Santa Catarina (LAMEB/UFSC) for technical assistance. IAVW received a fellowship from CAPES Foundation, Ministry of Education of Brazil. The funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Departamento de Bioquímica e Programa de Pós-Graduação em Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Florianópolis, Santa Catarina, 88040-900, Brazil

    Ingrid A. V. Wolin, Ana Paula M. Nascimento, Rodrigo Seeger, Gabriela G. Poluceno, Carla I. Tasca & Rodrigo Bainy Leal

  2. Departamento de Farmacologia e Programa de Pós-Graduação em Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Florianópolis, Santa Catarina, 88040-900, Brazil

    Alfeu Zanotto-Filho

  3. Departamento de Biologia Celular, Embriologia e Genética, Programa Pós-Graduação em Biologia Celular e do Desenvolvimento, Universidade Federal de Santa Catarina, Campus Universitário, Florianópolis, Santa Catarina, 88040-900, Brazil

    Claudia B. Nedel

  4. Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Ceará, CEP, 60020-181, BioMolLab, Fortaleza, Ceará, Brazil

    Sarah Elizabeth Gomes Correia, Messias Vital Oliveira, Vanir Reis Pinto-Junior, Vinicius Jose Silva Osterne, Kyria Santiago Nascimento & Benildo Sousa Cavada

  5. Departamento de Física, Universidade Federal do Ceará, Fortaleza, Ceará, CEP, 60020-181, Brazil

    Vanir Reis Pinto-Junior

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  1. Ingrid A. V. Wolin
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Correspondence to Rodrigo Bainy Leal.

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The authors have declared that there are no conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

Ethical approval

This study was performed in compliance with the Helsinki Declaration on ethical principles for handling human tissue specimens, with all Brazilian national regulations and requirements. Glioblastoma Multiforme (GBM1) cells were surgically isolated from a GBM tumor from a patient at Hospital Celso Ramos in Florianopolis, Santa Catarina, Brazil and cultured at Santa Catarina Federal University (UFSC/Brazil). All procedures, and patient consent forms were approved by the UFSC/Brazil, Human Research Ethics Committee (CEPSH protocol number 108.286). Primary astrocyte cultures were prepared from cerebral cortex male newborn Wistar rats. The animals were provided by the Animal Care Facility at the Federal University of Santa Catarina (UFSC). All procedures were approved by the Institutional Animal Care and Use Committee (CEUA/UFSC protocol number 2380161216). Rat C6 glioma cells (ATCC-CCL-107) and human U87 glioma cells (ATCC/ HTB-14) lineages were provided by the Cell Bank of Rio de Janeiro (RJ, Brazil).

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Wolin, I.A.V., Nascimento, A.P.M., Seeger, R. et al. The lectin DrfL inhibits cell migration, adhesion and triggers autophagy-dependent cell death in glioma cells. Glycoconj J 40, 47–67 (2023). https://doi.org/10.1007/s10719-022-10095-3

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