The role of autophagy in the death of L1210 leukemia cells initiated by the new antitumor agents, XK469 and SH80

Kessel, David; Reiners, John J.; Hazeldine, Stuart; Polin, Lisa; Horwitz, Jerome P.

doi:10.1158/1535-7163.mct-05-0386

Cited by 28 publications

(30 citation statements)

References 44 publications

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“…Cleavage of a caspase-3/7 substrate containing the DEVD sequence and a quenched fluorophore (Molecular Probes/Invitrogen, E13184) was measured as described previously. 45 Cells were collected at specified intervals after irradiation for the assay, which was done in triplicate. A micro Lowry assay (Sigma-Aldrich, B3934, F9252) was used to estimate protein concentrations, using bovine serum albumin as the standard.…”

Section: Methodsmentioning

confidence: 99%

ATG7 deficiency suppresses apoptosis and cell death induced by lysosomal photodamage

2012

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Section: Methodsmentioning

confidence: 99%

ATG7 deficiency suppresses apoptosis and cell death induced by lysosomal photodamage

2012

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“…Exposure to statins (Araki and Motojima, 2008) or the FTI lonafarnib (Pan et al, 2008) has been reported to induce autophagy in a variety of cell types. Although autophagy is generally perceived as being a prosurvival process, it has been linked to caspase-independent cell death (Bursch, 2001;Kessel et al, 2007;Scarlatti et al, 2009). The induction of autophagy is characterized by the accumulation of autophagosomes, which can be monitored by following the posttranslational addition of phosphatidylethanolamine to the cytosolic protein LC3-I to form LC3-II (Mizushima and Yoshimori, 2007).…”

Section: Downloaded Frommentioning

confidence: 99%

“…Comparisons of autophagic proficient and deficient cell lines indicate that stress-induced autophagy often plays a prosurvival function (Debnath et al, 2005;Elliott and Reiners, 2008;Scarlatti et al, 2009). Nevertheless, numerous examples have been published in which autophagy appears to contribute to cell death by a nonapoptotic mechanism, which has been termed class II death (Bursch, 2001;Kessel et al, 2007;Scarlatti et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Aborted Autophagy and Nonapoptotic Death Induced by Farnesyl Transferase Inhibitor and Lovastatin

Wojtkowiak

Sane

Kleinman

et al. 2011

J Pharmacol Exp Ther

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Exposure of the human malignant peripheral nerve sheath tumor cell lines STS-26T, ST88-14, and NF90-8 to nanomolar concentrations of both lovastatin and farnesyl transferase inhibitor (FTI)-1 but not to either drug alone induced cell death. ST88-14 and NF90-8 cells underwent apoptosis, yet dying STS-26T cells did not. FTI-1 cotreatment induced a strong and sustained autophagic response as indicated by analyses of microtubule-associated protein-1 light chain 3 (LC3)-II accumulation in STS-26T cultures. Extensive colocalization of LC3-positive punctate spots was observed with both lysosomeassociated membrane protein (LAMP)-1 and LAMP-2 (markers of late endosomes/lysosomes) in solvent or FTI-1 or lovastatintreated STS-26T cultures but very little colocalization in lovastatin/FTI-1-cotreated cultures. The absence of colocalization in the cotreatment protocol correlated with loss of LAMP-2 expression. Autophagic flux studies indicated that lovastatin/ FTI-1 cotreatment inhibited the completion of the autophagic program. In contrast, rapamycin induced an autophagic response that was associated with cytostasis but maintenance of viability. These studies indicate that cotreatment of STS-26T cells with lovastatin and FTI-1 induces an abortive autophagic program and nonapoptotic cell death.

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“…Upon starvation or drug stimuli, Bcl-2 can be phosphorylated by some upstream factors, for example, ERK, leading to release of Beclin-1 and induction of autophagy (19,20).…”

Section: Introductionmentioning

confidence: 99%

Activation of ERK–p53 and ERK-Mediated Phosphorylation of Bcl-2 Are Involved in Autophagic Cell Death Induced by the c-Met Inhibitor SU11274 in Human Lung Cancer A549 Cells

Liu

Yang

et al. 2012

J Pharmacol Sci

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Abstract. SU11274, a small molecule inhibitor of c-Met, was reported to induce apoptosis in human non-small-cell lung cancer (NSCLC) cells. However, SU11274-mediated autophagy in NSCLC cells has rarely been reported. The aim of this study was to elucidate the molecular mechanisms mediating SU11274-induced autophagy in NSCLC A549 cells. Here we reported that SU11274-induced autophagy was accompanied with an increase in the conversion of LC3-I to LC3-II and up-regulation of Beclin-1 expression. Subsequently, we also found that small interfering RNA against c-Met induced A549 cell autophagy while promotion of c-Met by hepatocyte growth factor (HGF) suppressed A549 cell autophagy. Inhibition of autophagy by 3-methyladenine (3-MA) suppressed SU11274-induced cell death, suggesting that SU11274-induced autophagy caused cell death. Further study showed that ERK and p53 were activated after SU11274 treatment. Interruption of ERK and p53 activities decreased SU11274-induced autophagy, and blocking of ERK by the specific inhibitor PD98059 suppressed SU11274-induced p53 activation. Moreover, ERK activation upregulated Beclin-1 expression through induction of Bcl-2 phosphorylation, but p53 did not induce Bcl-2 phosphorylation. In conclusion, inhibition of c-Met induced autophagic cell death, which was associated with ERK-p53 activation and ERK-mediated Bcl-2 phosphorylation in A549 cells.

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The role of autophagy in the death of L1210 leukemia cells initiated by the new antitumor agents, XK469 and SH80

Cited by 28 publications

References 44 publications

ATG7 deficiency suppresses apoptosis and cell death induced by lysosomal photodamage

ATG7 deficiency suppresses apoptosis and cell death induced by lysosomal photodamage

Aborted Autophagy and Nonapoptotic Death Induced by Farnesyl Transferase Inhibitor and Lovastatin

Activation of ERK–p53 and ERK-Mediated Phosphorylation of Bcl-2 Are Involved in Autophagic Cell Death Induced by the c-Met Inhibitor SU11274 in Human Lung Cancer A549 Cells

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