info:eu-repo/semantics/article
Pharmacological Rac1 inhibitors with selective apoptotic activity in human acute leukemic cell lines
Fecha
2017-10Registro en:
Cabrera, Maia Diana Eliana; Echeverría, Emiliana Beatriz; Remes Lenicov, Federico; Cardama, Georgina Alexandra; González, Nazareno; et al.; Pharmacological Rac1 inhibitors with selective apoptotic activity in human acute leukemic cell lines; Impact Journals LLC; Oncotarget; 8; 58; 10-2017; 98509-98523
1949-2553
CONICET Digital
CONICET
Autor
Cabrera, Maia Diana Eliana
Echeverría, Emiliana Beatriz
Remes Lenicov, Federico
Cardama, Georgina Alexandra
González, Nazareno
Davio, Carlos Alberto
Fernandez, Natalia Cristina
Lorenzano Menna, Pablo
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 patientderived leukemia cells but not on normal mononuclear cells. These results show the potential therapeutic benefits of targeting Rac1 pathway in hematopoietic malignancies.