Metformin Induces Apoptosis through AMPK-Dependent Inhibition of UPR Signaling in ALL Lymphoblasts
Figure 2
Metformin activates AMPK, Akt, and UPR signaling pathway proteins in ALL primary and cell line models.
A) Western blot analysis of proteins associated with AMPK, and Akt/mTOR signaling pathways in CCRF-CEM and NALM6 cells treated with metformin (MET, 2.5 and 5.0 mM) for 48 h. The density value of each band was normalized to β-actin level and expressed relative to control (shown as fold induction). B) Immunoblotting of UPR signaling factors in CCRF-CEM and NALM6 cells treated with metformin (MET, 2.5 and 5.0 mM) for 48 h. C) Western blots of AMPK, Akt/mTOR and UPR signaling proteins in representative sample of primary T- and Bp-ALL cells treated with metformin (MET, 10 mM) for 24 h. D) Western blot analysis of GRP78 expression in CCRF-CEM and NALM6 cells treated with metformin (MET, 10mM) and tunicamycin (TUN, 2.5 µg/ml for NALM6; 5.0 µg/ml for CCRF-CEM), either alone or in combination for 48 h.