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

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.

Copaifera spp. oleoresins impair Toxoplasma gondii infection in both human trophoblastic cells and human placental explants

“…The parasite cell cycle was analyzed by flow cytometry as previously described 69 , 70 , 86 , with some modifications. Briefly, BeWo cells were seeded at 1.0 × 10 6 cells/well in 6-well microplates.…”

Myosin Motors: Novel Regulators and Therapeutic Targets in Colorectal Cancer

“…Cellular activities of PCLP appear to be consistent with the known functional roles of class I myosins in regulating vesicle trafficking and actin cytoskeleton architecture. Thus, PCLP treatment perturbed lysosomal morphology in HeLa cells [183], as well as altered the endocytic trafficking and recycling of transforming growth factor (TGF)-β receptor and integrins in various human cancer and primary endothelial cells [184,185]. Furthermore, PCLP caused abnormal cytokinesis and cortical F-actin remodeling in zebrafish embryos [173] and inhibited the early morphogenic steps in chick embryos [174].…”

Motor Protein MYO1C is Critical for Photoreceptor Opsin Trafficking and Visual Function

“…We and others have previously shown that the natural compound pentachloropseudilin (PClP) acts as an allosteric inhibitor of MYO1C ATPase and motor activity [38][39][40][41][51][52][53].…”

“…To test whether the inhibition of MYO1C function by PCIP affects opsin trafficking, PCIP was retro-orbitaly injected (5mg/kg body weight) into the right eye of two-month old WT animals (n=2). At this concentration, PCIP was observed to inhibit all Myo1c isoforms without affecting non-Myo1 Myosins [35,38,40,41,[51][52][53][54][55][56]. The control set of WT animals (n=2) received retro-orbital injections of vehicle control (DMSO).…”