RESULTS: BKM120 potently induced elevation of autophagosome-bound type II LC3 (LC3-II) protein, particularly in cell lines insensitive to BKM120. The presence of the lysosomal protease inhibitor chloroquine further enhanced the levels of LC3-II. Hence, BKM120 induces autophagy. When combined with chloroquine, enhanced growth-inhibitory effects including induction of apoptosis were observed, suggesting that autophagy is a protective mechanism counteracting BKM120’s growth-inhibitory activity. Interestingly BKM120 increased p-ERK1/2 levels, suggesting that it activates MEK/ERK signaling. When blocking the activation of this signaling with MEK inhibitors or with knockdown of ERK1/2, the ability of BKM120 to increase LC3-II was attenuated and the growth-inhibitory effects including induction of apoptosis were accordingly enhanced, suggesting that the MEK/ERK activation contributes to BKM120-induced authophagy.