Src and PI3 K inhibitors affect the virulence factors of Entamoeba histolytica.
Protein kinases (PKs) of parasitic protozoa are being evaluated as drug targets. A large number of protein kinases within the protein kinome of Entamoeba histolytica strongly suggest that protein phosphorylation is a key component of pathogenesis regulation by this parasite. PI3 K and Src are kinases previously described in this parasite, but their role is poorly understood. Here, the effect of Src-1-inhibitor and PI3 K inhibitor (Wortmannin) on the virulence factors of E. histolytica was evaluated. Results show that both inhibitors affect the actin cytoskeleton and the amoebic movement. Also, the proteolytic activity is diminished by Wortmannin, but not by Src-inhibitor-1; however, the phagocytic capacity is diminished by Wortmannin and Src-1-inhibitor. Finally, we found that the virulence in vivo of E. histolytica is affected by Wortmannin but not by Src-1-inhibitor. This study opens the way for the design of anti-amoebic drugs based on kinase inhibition.
Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies, Av. IPN 2508, San Pedro Zacatenco, 07360, Mexico City, Mexico.
L
L
López-Contreras
V I
VI
Hernández-Ramírez
Y
Y
Flores-García
B
B
Chávez-Munguía
P
P
Talamás-Rohana
D008841:Actin Cytoskeleton / Q000187:drug effects; D000730:Androstadienes / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D004748:Entamoeba histolytica / Q000187:drug effects* / Q000201:enzymology* / Q000472:pathogenicity; D004749:Entamoebiasis / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D008297:Male; D010587:Phagocytosis / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D059748:Proteolysis / Q000187:drug effects; D037521:Virulence Factors / Q000378:metabolism*; D000077191:Wortmannin; D019061:src-Family Kinases / Q000378:metabolism
D000730:Androstadienes; D047428:Protein Kinase Inhibitors; D037521:Virulence Factors; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases; D000077191:Wortmannin