UNASSIGNED: @entity1502 ( @entity4045 ), a non-specific phosphodiesterase inhibitor is known to inhibit the growth of various @entity5 cells including @entity320 . Here in this study, we have found that @entity4045 induces autophagy in @entity1 @entity320 cell lines (A375 and MeWo). Induction of autophagy is associated with the increase in @entity10614 expression as knockdown of @entity10614 effectively inhibited @entity4045 mediated autophagy. A decrease in @entity3470 activation was also observed after @entity4045 treatment. We observed that autophagy was activated as a downstream effector mechanism of ER stress induced by @entity4045 . ER stress response was confirmed by upregulation of @entity5593 , @entity1477 and @entity3726 expression. @entity4045 treatment also resulted in an increase in intracellular @entity460 ( @entity141 ) level. @entity141 is the central player as blocking @entity141 by intracellular @entity460 chelator ( @entity11008 ) effectively inhibited the @entity4045 induced ER stress response as well as autophagy. Moreover, silencing of @entity3726 also resulted in autophagy inhibition with a decrease in @entity10614 expression. Collectively, @entity4045 triggers ER stress response followed by induction of autophagy via involvement of @entity141 > @entity3726 > @entity10614 signalling cascade. Interestingly, inhibition of intracellular @entity460 level by @entity11008 significantly increased @entity4045 mediated cell death by augmenting intrinsic apoptotic pathway. Inhibition of autophagy by the @entity10614 siRNA and pharmacological inhibitor, @entity503 also enhances @entity4045 induced cell death. Taken together, our results clearly indicate that activation of ER stress response and autophagy provides resistance to @entity4045 mediated apoptosis, and thus, interferes with the anticancer activity of @entity4045 in @entity1 @entity320 cells.

@entity1502 triggers autophagy via ER stress response that interferes with @entity1502 induced apoptosis in @entity1 XXXX cells.

@entity1 :: ('9606', 'Species') :: ['human'] @entity1477 :: ('3309', 'Gene') :: ['GRP78'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity3726 :: ('1649', 'Gene') :: ['CHOP'] @entity4045 :: ('D010852', 'Chemical') :: ['PTX'] @entity10614 :: ('9474', 'Gene') :: ['Atg5', 'ATG5'] @entity5593 :: ('2081', 'Gene') :: ['IRE-1a'] @entity3470 :: ('21977(Tax:10090)', 'Gene') :: ['mTOR'] @entity1502 :: ('MESH:D010431', 'Chemical') :: ['Pentoxifylline'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)'] @entity503 :: ('MESH:D002738', 'Chemical') :: ['chloroquine'] @entity11008 :: ('MESH:C070379', 'Chemical') :: ['BAPTA-AM'] @entity320 :: ('MESH:D008545', 'Disease') :: ['melanoma']
@entity320 :: (MESH:D008545,Disease) :: ['melanoma']
