1. Academic Validation
  2. Pharmacological Rac1 inhibitors with selective apoptotic activity in human acute leukemic cell lines

Pharmacological Rac1 inhibitors with selective apoptotic activity in human acute leukemic cell lines

  • Oncotarget. 2017 Oct 4;8(58):98509-98523. doi: 10.18632/oncotarget.21533.
Maia Cabrera 1 Emiliana Echeverria 1 Federico Remes Lenicov 2 Georgina Cardama 3 Nazareno Gonzalez 3 Carlos Davio 1 Natalia Fernández  # 1 Pablo Lorenzano Menna  # 3
Affiliations

Affiliations

  • 1 Instituto de Investigaciones Farmacológicas, Facultad de Farmacia y Bioquímica (ININFA-UBA CONICET), Buenos Aires, Argentina.
  • 2 Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, Facultad de Medicina, (INBIRS-UBA-CONICET), Buenos Aires, Argentina.
  • 3 Laboratorio de Oncología Molecular, Universidad Nacional de Quilmes, Buenos Aires, Argentina.
  • # Contributed equally.
Abstract

Rac1 GTPase has long been recognized as a critical regulatory protein in different cellular and molecular processes involved in Cancer progression, including acute myeloid leukemia. Here we show the antitumoral activity of ZINC69391 and 1A-116, two chemically-related Rac1 pharmacological inhibitors, on a panel of four leukemic cell lines representing different levels of maturation. Importantly, we show that the main mechanism involved in the antitumoral effect triggered by the Rac1 inhibitors comprises the induction of the mitochondrial or intrinsic apoptotic pathway. Interestingly, Rac1 inhibition selectively induced Apoptosis on patient-derived leukemia cells but not on normal mononuclear cells. These results show the potential therapeutic benefits of targeting Rac1 pathway in hematopoietic malignancies.

Keywords

1A-116; Rac1; ZINC69391; acute myeloid leukemia; apoptosis.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-102078
    99.76%, Rac1-GEF Interaction Inhibitor