BAX-dependent mitochondrial pathway mediates the crosstalk between ferroptosis and apoptosis

Lee, Young Sun; Kalishwaralal, Kalimuthu; Park, Yong Seok; Luo, Xu; Choudry, M. Haroon A.; Bartlett, David L.

doi:10.1007/s10495-020-01627-z

Cited by 66 publications

(43 citation statements)

References 20 publications

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“…Consistently, Lee et al. described that although combination therapy with TRAIL and other compounds could make human colon cancer HCT116 cell line susceptible to TRAIL, Bax-deficient cells but not Bak-deficient cells, restored their resistance to TRAIL ( 50 ). In sum, these findings imply that the TRAIL-induced apoptosis is closely linked to Bax-mediated mitochondria-dependent pathway.…”

Section: Mechanisms Of Cancer Resistances To Trailmentioning

confidence: 85%

RETRACTED: Harnessing TRAIL-Induced Apoptosis Pathway for Cancer Immunotherapy and Associated Challenges

et al. 2021

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The immune cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted rapidly evolving attention as a cancer treatment modality because of its competence to selectively eliminate tumor cells without instigating toxicity in vivo. TRAIL has revealed encouraging promise in preclinical reports in animal models as a cancer treatment option; however, the foremost constraint of the TRAIL therapy is the advancement of TRAIL resistance through a myriad of mechanisms in tumor cells. Investigations have documented that improvement of the expression of anti-apoptotic proteins and survival or proliferation involved signaling pathways concurrently suppressing the expression of pro-apoptotic proteins along with down-regulation of expression of TRAILR1 and TRAILR2, also known as death receptor 4 and 5 (DR4/5) are reliable for tumor cells resistance to TRAIL. Therefore, it seems that the development of a therapeutic approach for overcoming TRAIL resistance is of paramount importance. Studies currently have shown that combined treatment with anti-tumor agents, ranging from synthetic agents to natural products, and TRAIL could result in induction of apoptosis in TRAIL-resistant cells. Also, human mesenchymal stem/stromal cells (MSCs) engineered to generate and deliver TRAIL can provide both targeted and continued delivery of this apoptosis-inducing cytokine. Similarly, nanoparticle (NPs)-based TRAIL delivery offers novel platforms to defeat barricades to TRAIL therapeutic delivery. In the current review, we will focus on underlying mechanisms contributed to inducing resistance to TRAIL in tumor cells, and also discuss recent findings concerning the therapeutic efficacy of combined treatment of TRAIL with other antitumor compounds, and also TRAIL-delivery using human MSCs and NPs to overcome tumor cells resistance to TRAIL.

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Section: Mechanisms Of Cancer Resistances To Trailmentioning

confidence: 85%

RETRACTED: Harnessing TRAIL-Induced Apoptosis Pathway for Cancer Immunotherapy and Associated Challenges

et al. 2021

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“…In addition, Bax and Bcl-2 are potentially central regulators of apoptosis, necroptosis, and ferroptosis as they serve as crosstalk between these cell death pathways [ 45 – 48 ]. Our data showed that Bax/Bcl-2 was remarkably decreased by all cell death inhibitors and might involve in neuroprotection following cardiac I/R injury.…”

Section: Discussionmentioning

confidence: 99%

Cell death inhibitors protect against brain damage caused by cardiac ischemia/reperfusion injury

et al. 2021

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Cognitive impairment has been reported in patients with myocardial infarction despite a successful reperfusion therapy. Several modes of cell death are involved in brain damage during cardiac ischemia/reperfusion (I/R) injury. Although apoptosis, necroptosis, and ferroptosis inhibitors provided neuroprotection against cerebral I/R injury, the effects of these cell death inhibitors on the brain following cardiac I/R injury have never been investigated. We hypothesized that apoptosis, necroptosis, and ferroptosis inhibitors attenuate brain damage following cardiac I/R injury. One-hundred and twenty-six male rats were used: 6 rats were assigned to sham operation and 120 rats were subjected to 30-min regional cardiac ischemia and 120-min reperfusion. Rats in cardiac I/R group were pretreated with either vehicle (n = 12) or one of cell death inhibitors. Rats treated with apoptosis, necroptosis, or ferroptosis inhibitor were subdivided into three different doses including low (L), medium (M), and high (H) doses (n = 12/group). Z-VAD, necrostatin-1 (Nec-1), and ferrostatin-1 (Fer-1) were used as apoptosis, necroptosis, and ferroptosis inhibitor, respectively. Rats were sacrificed at the end of reperfusion, and the brain was used to analyze dendritic spine density, Alzheimer’s disease (AD)-related proteins, blood–brain barrier (BBB) tight junction proteins, mitochondrial function, inflammation, and cell death. Our data showed that cardiac I/R led to brain damage and only apoptosis occurred in the hippocampus after cardiac I/R injury. In the cardiac I/R group, treatment with M-Z-VAD and all doses of Nec-1 decreased hippocampal apoptosis and amyloid beta aggregation, thereby reducing dendritic spine loss. M- and H-Fer-1 also reduced dendritic spine loss by suppressing ACSL4, TNF-α, amyloid beta, and tau hyperphosphorylation. Moreover, Bax/Bcl-2 was decreased in all treatment regimen except L-Z-VAD. Additionally, M-Z-VAD and M-Fer-1 partially attenuated mitochondrial dysfunction. Only L-Nec-1 preserved BBB proteins. In conclusion, cell death inhibitors prevented hippocampal dendritic spine loss caused by cardiac I/R injury through different mechanisms.

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“…In our recent article [1], we report that ER stress response plays a pivotal role in the crosstalk between ferroptosis and apoptosis. Dr. Yoshida constructively criticizes that TRAIL treatment alone leads to JC-1 aggregation and combined treatment of TRAIL and erastin results in mitochondrial depolarization which is indicated by an increase in JC-1 fluorescence intensity.…”

Section: Replymentioning

confidence: 99%

The interplay between apoptosis and ferroptosis mediated by ER stress

Lee

2020

Apoptosis

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BAX-dependent mitochondrial pathway mediates the crosstalk between ferroptosis and apoptosis

Cited by 66 publications

References 20 publications

RETRACTED: Harnessing TRAIL-Induced Apoptosis Pathway for Cancer Immunotherapy and Associated Challenges

RETRACTED: Harnessing TRAIL-Induced Apoptosis Pathway for Cancer Immunotherapy and Associated Challenges

Cell death inhibitors protect against brain damage caused by cardiac ischemia/reperfusion injury

The interplay between apoptosis and ferroptosis mediated by ER stress

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