Hypoxia induces autophagic cell death in apoptosis-competent cells through a mechanism involving BNIP3

Azad, Meghan B.; Chen, Yongqiang; Henson, Elizabeth S.; Cizeau, Jeannick; McMillan-Ward, Eileen M.; Israels, Sara J.; Gibson, Spencer B.

doi:10.4161/auto.5278

Cited by 320 publications

(289 citation statements)

References 39 publications

(70 reference statements)

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“…It seems that BNIP3 can induce autophagy by interacting with RheB, resulting in mTOR inhibition [17]. Moreover, the involvement of BNIP3 in later stages of autophagy, such as autophagosome-lysosome fusion, has also been described [16]. In this work, we have studied the involvement of BNIP3 in the protective effect of hypoxia against apoptosis for several reasons.…”

Section: Discussionmentioning

confidence: 98%

“…shown that hypoxia induces autophagy through the AMPK activation [49] but the main mechanism of induction of autophagy by hypoxia requires HIF-1 and BNIP3 [10,16]. The reason of this discrepancy is not known.…”

Section: Discussionmentioning

confidence: 99%

“…To explain why etoposide-induced autophagy does not have the same consequences under normoxia and under hypoxia, we investigated the role of BNIP3, a hypoxia-induced protein for which an involvement in autophagy has been clearly demonstrated [16]. BNIP3 is a BH3-only protein encoded by a HIF-1-target gene [33].…”

Section: Effect Of Bnip3 On the Resistance Against Etoposide-induced mentioning

confidence: 99%

“…However, the precise mechanisms involved are still poorly understood. It seems that BNIP3 could be involved in autophagosome-lysosome fusion or in earlier stages such as Beclin-1 activation and mTOR inhibition [10,16,17].…”

Section: Introductionmentioning

confidence: 99%

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BNIP3 protects HepG2 cells against etoposide-induced cell death under hypoxia by an autophagy-independent pathway

Cosse

Rommelaere

Ninane

et al. 2010

Biochemical Pharmacology

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Tumor hypoxia is a common characteristic of most solid tumors and is correlated with poor prognosis for patients partly because hypoxia promotes resistance to cancer therapy. Hypoxia selects cancer cells that are resistant to apoptosis and allows the onset of mechanisms that promote cancer cells survival including autophagy. Previously, we showed that human hepatoma HepG2 cells were protected under hypoxia against the etoposide-induced apoptosis.In this study, respective putative contribution of autophagy and BNIP3 in the protection conferred by hypoxia against the etoposide-induced apoptosis was investigated. We report that autophagy is induced by etoposide, a process that is not affected by hypoxic conditions. Using Atg5 siRNA, we show that etoposide-induced autophagy promotes apoptotic cell death under normoxia but not under hypoxia. Then, we investigated whether the hypoxia-induced protein BNIP3 could explain the different effect of autophagy on cell death under hypoxia or normoxia. We show that the silencing of BNIP3 does not affect autophagy whatever the pO 2 but participates in the protective effect of hypoxia against etoposide-induced apoptosis.Together, these results suggest that autophagy might be involved in etoposide-induced cell death only under normoxia and that BNIP3 is a major effector of the protective mechanism conferred by hypoxia to protect cancer cells against etoposide-induced apoptotic cell death.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Effect Of Bnip3 On the Resistance Against Etoposide-induced mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

BNIP3 protects HepG2 cells against etoposide-induced cell death under hypoxia by an autophagy-independent pathway

Cosse

Rommelaere

Ninane

et al. 2010

Biochemical Pharmacology

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“…It was the manifestation of autophagosomes in dying cells exhibiting features distinct from apoptosis that led scientists to suggest a death-promoting role for autophagy (Levine and Yuan, 2005). In vitro studies found the abrogation of autophagy by 3-methyladenine (Schwarze and Seglen, 1985;Azad et al, 2008) or knockdown of autophagy-related genes, beclin 1 and atg5 or atg7, (Shimizu et al, 2004;Yu et al, 2004) prevented cell death. In vivo, chemotherapy and radiotherapy are known to induce both cell death and autophagy in tumour cells, and autophagy has been observed to confer a tumour suppressive effect in various animal models (see subsequent section).…”

Section: Autophagymentioning

confidence: 99%

New frontiers in promoting tumour cell death: targeting apoptosis, necroptosis and autophagy

2012

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PBK attenuates paclitaxel‐induced autophagic cell death by suppressing p53 in H460 non‐small‐cell lung cancer cells

Park

Lee

et al. 2020

FEBS Open Bio

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PDZ‐binding kinase (PBK) has previously been shown to mediate chemoresistance of cancer cells to anticancer drugs. However, it remains unclear how PBK regulates paclitaxel‐induced cancer cell death. Here, we demonstrate that PBK hinders paclitaxel‐mediated autophagic cell death in H460 non‐small‐cell lung cancer cells. PBK knockdown increased apoptosis, autophagy, p53 level, and LC3 puncta upon paclitaxel treatment. Moreover, p53 expression facilitated an increase in the LC3‐II/LC3‐I ratio in response to paclitaxel, and PBK knockdown augmented paclitaxel‐mediated p53 transcriptional activity. Meanwhile, paclitaxel induced PBK‐mediated p53 nuclear export and its subsequent ubiquitination in control cells, but not in PBK knockdown cells. We conclude that PBK hampers paclitaxel‐induced autophagic cell death by suppressing p53, suggesting a potential role of PBK in p53‐mediated H460 cell death.

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Hypoxia induces autophagic cell death in apoptosis-competent cells through a mechanism involving BNIP3

Cited by 320 publications

References 39 publications

BNIP3 protects HepG2 cells against etoposide-induced cell death under hypoxia by an autophagy-independent pathway

BNIP3 protects HepG2 cells against etoposide-induced cell death under hypoxia by an autophagy-independent pathway

New frontiers in promoting tumour cell death: targeting apoptosis, necroptosis and autophagy

PBK attenuates paclitaxel‐induced autophagic cell death by suppressing p53 in H460 non‐small‐cell lung cancer cells

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