Oxidative stress induced by Pollonein-LAAO, a new L-amino acid oxidase from Bothrops moojeni venom, prompts prostate tumor spheroid cell death and impairs the cellular invasion process in vitro.
[en] Cancer cells produce abnormal levels of reactive oxygen species (ROS) that contribute to promote their malignant phenotype. In this framework, we hypothesized that the change in ROS concentration above threshold could impair key events of prostate cancer cells (PC-3) progression. Our results demonstrated that Pollonein-LAAO, a new L-amino acid oxidase obtained from Bothrops moojeni venom, was cytotoxic to PC-3 cells in two-dimensional and in tumor spheroid assays. Pollonein-LAAO was able to increase the intracellular ROS generation that culminates in cell death from apoptosis by both intrinsic and extrinsic pathways due to the up-regulation of TP53, BAX, BAD, TNFRSF10B and CASP8. Additionally, Pollonein-LAAO reduced mitochondrial membrane potential and caused G0/G1 phase to delay, due to the up-regulation of CDKN1A and the down-regulation of the expression of CDK2 and E2F. Interestingly, Pollonein-LAAO inhibited critical steps of the cellular invasion process (migration, invasion and adhesion), due to the down-regulation of SNAI1, VIM, MMP2, ITGA2, ITGAV and ITGB3. Furthermore, the Pollonein-LAAO effects were associated with the intracellular ROS production, since the presence of catalase restored the invasiveness of PC-3 cells. In this sense, this study contributes to the potential use of Pollonein-LAAO as ROS-based agent to enhance the current understanding of cancer treatment strategies.
Disciplines :
Chemistry
Author, co-author :
Polloni, Lorena; Institute of Biotechnology, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil. Electronic address: polloni.lorena@gmail.com
Costa, Tássia Rafaella; Institute of Biotechnology, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil
Morais, Lorena Pinheiro; Institute of Biomedical Sciences, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil
Borges, Bruna Cristina; Institute of Biomedical Sciences, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil
Teixeira, Samuel Cota; Institute of Biomedical Sciences, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil
de Melo Fernandes, Thales Alves; Institute of Biotechnology, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil
Correia, Lucas Ian Veloso; Institute of Biotechnology, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil
Bastos, Luciana Machado; Institute of Biotechnology, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil
Gobbi Amorim, Fernanda ; Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.) ; Université de Liège - ULiège > Molecular Systems (MolSys)
Quinton, Loïc ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie biologique ; Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.)
Soares, Andreimar Martins; Oswaldo Cruz Foundation (FIOCRUZ) Rondônia, Federal University of Rondônia (UNIR), and National Institute of Science and Technology of Epidemiology of the Western Amazon (INCT-EPIAMO), Porto Velho, RO, Brazil
Silva, Marcelo José Barbosa; Institute of Biomedical Sciences, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil
Ferro, Eloisa Amália Vieira; Institute of Biomedical Sciences, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil
Lopes, Daiana Silva; Multidisciplinary Institute for Health, Federal University of Bahia - UFBA, Vitoria da Conquista, BA, Brazil
de Melo Rodrigues Ávila, Veridiana; Institute of Biotechnology, Federal University of Uberlândia - UFU, Uberlândia, MG, Brazil. Electronic address: veridiana@ufu.br
Oxidative stress induced by Pollonein-LAAO, a new L-amino acid oxidase from Bothrops moojeni venom, prompts prostate tumor spheroid cell death and impairs the cellular invasion process in vitro.
The present study was supported by the Federal University of Uberlândia (UFU) , the Coordination for the Improvement of Higher Education Personnel (CAPES) , the National Council for Scientific and Technological Development (CNPq) , the Foundation for Support to the Development of Scientific and Technological Actions of Minas Gerais state (FAPEMIG) , the National Institute of Science and Technology in Theranostics and Nanobiotechnology (INCT-TeraNano) , the Foundation for Support to the Development of Scientific and Technological Actions of the Rondônia Research (FAPERO) , PDTIS/FIOCRUZ platforms , the Center for the Study of Biomolecules Applied to Health-CEBio/FIOCRUZ-RO and the Research Excellence Program (PROEP-FIOCRUZ) .The authors thank the GIGA-Proteomics platform (ERDF funding) for the technical support, specially Maximilien Fléron and Dominique Baiwir from GIGA-Proteomics Facility of the University of Liège for the use of the mass spectrometer instruments. Q-Exactive mass spectrometer was funded by ERDF and the Walloon Region grant and Peaks X+ version Studio 10.5 software were funded by ERDF grant: BIOMED HUB Technology Support (number 2.2.1/996 ). The authors thank the Felipe Andrés Cordero da Luz, Ph. D., for perform partial eta squared statistical analysis.The present study was supported by the Federal University of Uberlândia (UFU), the Coordination for the Improvement of Higher Education Personnel (CAPES), the National Council for Scientific and Technological Development (CNPq), the Foundation for Support to the Development of Scientific and Technological Actions of Minas Gerais state (FAPEMIG), the National Institute of Science and Technology in Theranostics and Nanobiotechnology (INCT-TeraNano), the Foundation for Support to the Development of Scientific and Technological Actions of the Rondônia Research (FAPERO), PDTIS/FIOCRUZ platforms, the Center for the Study of Biomolecules Applied to Health-CEBio/FIOCRUZ-RO and the Research Excellence Program (PROEP-FIOCRUZ).The authors thank the GIGA-Proteomics platform (ERDF funding) for the technical support, specially Maximilien Fléron and Dominique Baiwir from GIGA-Proteomics Facility of the University of Liège for the use of the mass spectrometer instruments. Q-Exactive mass spectrometer was funded by ERDF and the Walloon Region grant and Peaks X+ version Studio 10.5 software were funded by ERDF grant: BIOMED HUB Technology Support (number 2.2.1/996). The authors thank the Felipe Andrés Cordero da Luz, Ph. D. for perform partial eta squared statistical analysis.
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