AICAR induces differentiation of acute myeloid leukemia cells (CROSBI ID 603802)
Prilog sa skupa u časopisu | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Lalić, Hrvoje ; Dembitz, Vilma ; Lukinović-Škudar, Vesna ; Banfić, Hrvoje ; Višnjić, Dora
engleski
AICAR induces differentiation of acute myeloid leukemia cells
Pharmacological modulators of AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway have been reported to exert antiproliferative effects in leukemia, but their role in differentiation is less explored. The aim of this study was to test for the effects of AMPK/ mTOR modulators in combination with differentiating agents in AML, especially in non- APL cell lines. Rapamycin alone had cytostatic effects but enhanced ATRA-mediated differentiation and DMSO- mediated growth arrest and apoptosis. AMPK activators, AICAR and metformin, significantly reduce the number of viable cells. Morphologic and FACS analysis shows the significant increase in apoptosis in cells treated with AICAR. Western blot analysis confirms that both agents activate AMPK and inhibit mTOR activity. AICAR enhances ATRA-mediated differentiation of NB4, a typical APL cell line. In U937 cells, AICAR alone induces the expression of cell surface markers associated with mature monocytes and macrophages. In both cell lines, AICAR increases the activity of MAPK, and the increase in the expression of CD64 and CD14 is inhibited in the presence of MAPK and AMPK inhibitors. These results suggest that a strategy using combination of differentiation agents with drugs targeting AMPK/mTOR may improve differentiation therapy for non-APL AML.
AICAR; differentiation; acute myeloid leukemia
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Podaci o prilogu
38-x.
2013.
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objavljeno
Podaci o matičnoj publikaciji
Periodicum biologorum
Vitale, Branko
Zagreb:
0031-5362
Podaci o skupu
3. Congress of Croatian Physiological Society and 1. Regional Congress of the Physiological Societies
poster
13.09.2013-15.09.2013
Rijeka, Hrvatska
Povezanost rada
Temeljne medicinske znanosti