Pentachloropseudilin impairs angiogenesis by disrupting the actin cytoskeleton, integrin trafficking and the cell cycle
Teixeira, Samuel Cota; Lopes, Daiana Silva; Silva, Marcelo Santos da ; Luz, Felipe Andrés Cordero da; Gimenes, Sarah Natalie Cirilo ; Borges, Bruna Cristina; Silva, Aline Alves da; Martins, Flávia Alves; Santos, Marlus Alves dos; Teixeira, Thaise Lara; Oliveira, Ricardo A.; Ávila, Veridiana de Melo Rodrigues; Silva, Marcelo José Barbosa; Elias, Maria Carolina ; Martin, René; Silva, Claudio Vieira da; Knölker, Hans‐Joachim
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.
angiogenesis; cell signaling; cytoskeleton; inhibitors; myosin 1; pentachloropseudilin
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- Teixeira, Samuel CotaLopes, Daiana SilvaSilva, Marcelo Santos da, et al. Chembiochem. 2019 Sept;20(18):2390-2401. Available at: https://repositorio.butantan.gov.br/handle/butantan/3196.
- Teixeira, Samuel Cota, et al. Chembiochem. Weinheim. v. 20, n. 18, p. 2390-2401, set. 2020. Disponível em: https://repositorio.butantan.gov.br/handle/butantan/3196.
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