Roles of the Akt/mTOR/p70S6K and ERK1/2 Signaling Pathways in Curcumin-Induced Autophagy

cAMP induces autophagy via a novel pathway involving ERK, cyclin E and Beclin 1

“…The Akt-mTOR-p70S6K pathway and the MEK-ERK pathway are well-known regulators of autophagy in mammalian cells. 6,9,10,14 Figure 2. inhibition of early autophagosome formation prevents cAMP-induced autophagic flux. (A) Ascs were pretreated with the class iii Pi3K inhibitor 3-methyladenine (3-MA, 10 mM) for 30 min prior to treatment with or without PGe 2 (75 μM) for 68 h. e64d (10 μg/ml) and pepstatin A (10 μg/ml) were added to the cells 48 h before harvesting.…”

“…6,9,10 The two former pathways have been shown to inhibit autophagy, 11,12 whereas activation of ERK can both stimulate or inhibit autophagy, depending on the cell type. 9,[13][14][15] Interestingly, activation of the cyclic AMP (cAMP)/protein kinase A (PKA) pathway is known to either inhibit or activate ERK in a cell-type specific manner, [16][17][18][19][20] but in these studies the changes in ERK-activation have not been related to autophagy. In fact, only inhibition of autophagy has been observed upon activation of the cAMP/PKA pathway in the cell types studied so far.…”

A Non-canonical MEK/ERK Signaling Pathway Regulates Autophagy via Regulating Beclin 1

“…Recent studies show that ERK up-regulates starvationcaused autophagy by down-regulating Akt/mTOR/S6K (27), but the molecular link between this pathway and the basis of autophagy machinery remains largely unclear. We observed here that activation of MEK/ERK coincided with up-regulation of Beclin 1 and autophagic responses, and MEK/ERK was activated by AMPK but not Raf1 in response to autophagy stimuli.…”

“…Diverse signaling pathways have been reported in the regulation of autophagy in mammalian cells (26,27). In contrast to yeast, mammalian cells regulate autophagy via both class I and class III PI3K.…”

Autophagy-associated Targeting Pathways of Natural Products during Cancer Treatment

“…In contrast, in the presence of autophagy inhibitor Bafilomycin A1, the curcumin-induced death of K562 cells is obviously inhibited, suggesting that curcumin can induce autophagy and K562 cell death. In glioblastoma cells, curcumin can inhibit Akt/p70S6K signal pathway, activate extracellular signal-regulated kinases (ERK1/2), and finally induce autophagy (Shinojima et al, 2007). It can induce the generation of reactive oxygen species (ROS), up-regulate the expression of Beclin 1 and p53, activate autophagy, and eventually result in the death of human colon cancer cells (Lee et al, 2011).…”