2. Academic Validation
  3. Pentachloropseudilin Impairs Angiogenesis by Disrupting the Actin Cytoskeleton, Integrin Trafficking and the Cell Cycle

Pentachloropseudilin Impairs Angiogenesis by Disrupting the Actin Cytoskeleton, Integrin Trafficking and the Cell Cycle

  • Chembiochem. 2019 Sep 16;20(18):2390-2401. doi: 10.1002/cbic.201900203.
Samuel Cota Teixeira 1,  Daiana Silva Lopes 2,  Marcelo Santos da Silva 3 4,  Felipe Andrés Cordero da Luz 1,  Sarah Natalie Cirilo Gimenes 5,  Bruna Cristina Borges 1,  Aline Alves da Silva 1,  Flávia Alves Martins 1,  Marlus Alves Dos Santos 1,  Thaise Lara Teixeira 1,  Ricardo A Oliveira 6,  Veridiana de Melo Rodrigues Ávila 7,  Marcelo José Barbosa Silva 1,  Maria Carolina Elias 3,  René Martin 8,  Claudio Vieira da Silva 1,  Hans-Joachim Knölker 8
Affiliations

Affiliations

  • 1 Department of Immunology, Biomedical Sciences Institute, Federal University of Uberlândia, Rua Piauí, Bloco 2B, sala 200, Campus Umuarama, Uberlândia, 38400-902, MG, Brazil.
  • 2 Multidisciplinary Institute of Health, Anísio Teixeira Campus, Federal University of Bahia, Rua Hormindo Barros, 58, Candeias, Vitória da Conquista, 45029-094, BA, Brazil.
  • 3 Special Laboratory of Cell Cycle (LECC), Center of Toxins, Immune Response and Cell Signaling (CeTICS), Butantan Institute, Av. Vital Brasil, 1500 - Butantã, São Paulo, 05503-900, SP, Brazil.
  • 4 The Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, Sir Graeme Davies Building, University of Glasgow, 120 University Place, Glasgow, G12 8TA, UK.
  • 5 Imunopathology Laboratory, Butantan Institute, Av. Vital Brasil, 1500 - Butantã, São Paulo, 05503-900, SP, Brazil.
  • 6 Medical School, Federal University of Uberlândia, Av. Pará, Bloco 2u, 1720 - Umuarama, Uberlândia, 38400-902, MG, Brazil.
  • 7 Institute of Biotechnology, Federal University of Uberlândia, Av. Pará, 1720 - Bloco 2E - Sala(s) 246 - Campus Umuarama, Uberlândia, 38405-320, MG, Brazil.
  • 8 Fakultät Chemie, Technische Universität Dresden, Bergstraße 66, 01069, Dresden, Germany.
PMID: 31026110 DOI: 10.1002/cbic.201900203
Abstract

Class 1 myosins (Myo1s) were the first unconventional myosins identified and humans have eight known Myo1 isoforms. The Myo1 family is involved in the regulation of gene expression, cytoskeletal rearrangements, delivery of proteins to the cell surface, cell migration and spreading. Thus, the important role of Myo1s in different biological processes is evident. In this study, we have investigated the effects of pentachloropseudilin (PClP), a reversible and allosteric potent inhibitor of Myo1s, on angiogenesis. We demonstrated that treatment of cells with PClP promoted a decrease in the number of vessels. The observed inhibition of angiogenesis is likely to be related to the inhibition of cell proliferation, migration and adhesion, as well as to alteration of the actin Cytoskeleton pattern, as shown on a PClP-treated HUVEC cell line. Moreover, we also demonstrated that PClP treatment partially prevented the delivery of integrins to the plasma membrane. Finally, we showed that PClP caused DNA strand breaks, which are probably repaired during the cell cycle arrest in the G1 phase. Taken together, our results suggest that Myo1s participate directly in the angiogenesis process.

Keywords

angiogenesis; cell signaling; cytoskeleton; inhibitors; myosin 1; pentachloropseudilin.

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