INVESTIGADORES
GONZALEZ Nazareno
artículos
Título:
Pharmacological Rac1 inhibitors with selective apoptotic activity in human acute leukemic cell lines
Autor/es:
MAIA CABRERA; EMILIANA ECHEVERRIA; FEDERICO REMES LENICOV; GEORGINA CARDAMA; NAZARENO GONZALEZ; CARLOS DAVIO; NATALIA FERNANDEZ; PABLO LORENZANO MENNA
Revista:
Oncotarget
Editorial:
Impact Journals
Referencias:
Año: 2017
ISSN:
1949-2553
Resumen:
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.