Research Papers:
Pharmacological Rac1 inhibitors with selective apoptotic activity in human acute leukemic cell lines
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Abstract
Maia Cabrera1, Emiliana Echeverria1, Federico Remes Lenicov2, Georgina Cardama3, Nazareno Gonzalez3, Carlos Davio1, Natalia Fernández1,* and Pablo Lorenzano Menna3,*
1Instituto de Investigaciones Farmacológicas, Facultad de Farmacia y Bioquímica (ININFA-UBA CONICET), Buenos Aires, Argentina
2Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, Facultad de Medicina, (INBIRS-UBA-CONICET), Buenos Aires, Argentina
3Laboratorio de Oncología Molecular, Universidad Nacional de Quilmes, Buenos Aires, Argentina
*These authors have contributed equally to this work
Correspondence to:
Pablo Lorenzano Menna, email: [email protected]
Keywords: Rac1; acute myeloid leukemia; apoptosis; ZINC69391; 1A-116
Received: November 25, 2016 Accepted: July 18, 2017 Published: October 04, 2017
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.
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PII: 21533