Antitumor Effect of 5-Aminolevulinic Acid Through Ferroptosis in Esophageal Squamous Cell Carcinoma

Shishido, Yuji; Amisaki, Masataka; Matsumi, Yoshiaki; Yakura, Haruna; Nakayama, Yuji; Miyauchi, Wataru; Miyatani, Kozo; Matsunaga, Tomoyuki; Hanaki, Takehiko; Kihara, Kyoichi; Yamamoto, Manabu; Tokuyasu, Naruo; Takano, Shuichi; Sakamoto, Teruhisa; Honjo, Soichiro; Hasegawa, Toshimichi; Fujiwara, Yoshiyuki

doi:10.1245/s10434-020-09334-4

Cited by 34 publications

(35 citation statements)

References 37 publications

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“…Ferroptosis, as an alternative approach of inducing cell death by lipid peroxidation, has attracted much attention to overcome some of the challenges associated to drug-resistant cancers [ 23 ]. Recently, ferroptosis has also been associated with PDT [ 16 , 24 , 25 ]. Our group has focused on the development of PSilQ nanoparticles as a photosensitizer-delivery platform for PDT [ 5 , 6 , 7 , 8 , 9 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, the addition of the phospholipid radical-trapping agent ferrostatin-1 reduced the phototoxicity exerted by PpIX-PSilQ NPs. This significant impact of ferrostatin-1 in the PDT performance of both PpIX-PSilQ nanoparticles and PpIX gives a clear indication that ferroptosis is an important cell death mechanism in their PDT performance [ 24 , 25 , 43 , 45 ]. Overall, these results are convincing arguments to support the hypothesis that ferroptosis is one of the main cell death mechanisms triggered by PSilQ nanoparticle-mediated photodynamic therapy.…”

Section: Discussionmentioning

confidence: 99%

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Light-Activated Protoporphyrin IX-Based Polysilsesquioxane Nanoparticles Induce Ferroptosis in Melanoma Cells

et al. 2021

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The use of nanoparticle-based materials to improve the efficacy of photodynamic therapy (PDT) to treat cancer has been a burgeoning field of research in recent years. Polysilsesquioxane (PSilQ) nanoparticles with remarkable features, such as high loading of photosensitizers, biodegradability, surface tunability, and biocompatibility, have been used for the treatment of cancer in vitro and in vivo using PDT. The PSilQ platform typically shows an enhanced PDT performance following a cell death mechanism similar to the parent photosensitizer. Ferroptosis is a new cell death mechanism recently associated with PDT that has not been investigated using PSilQ nanoparticles. Herein, we synthesized a protoporphyrin IX (PpIX)-based PSilQ platform (PpIX-PSilQ NPs) to study the cell death pathways, with special focus on ferroptosis, during PDT in vitro. Our data obtained from different assays that analyzed Annexin V binding, glutathione peroxidase activity, and lipid peroxidation demonstrate that the cell death in PDT using PpIX-PSilQ NPs is regulated by apoptosis and ferroptosis. These results can provide alternative approaches in designing PDT strategies to enhance therapeutic response in conditions stymied by apoptosis resistance.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Light-Activated Protoporphyrin IX-Based Polysilsesquioxane Nanoparticles Induce Ferroptosis in Melanoma Cells

et al. 2021

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“…Ferroptosis initiation and execution lie at the intersection of glutathione metabolism, lipid peroxidation of PUFAs, iron metabolism and mitochondrial function (Stockwell et al, 2017). A previous study reported that upregulation of GPX4 and downregulation of HMOX1 were poor prognostic factors for ESCC (Shishido et al, 2020). Another study found that DNAJB6 level was negative related to lymph node metastasis in ESCC patient (Jiang et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…The efficacy of cancer suppression by ferroptosis inducers in various studies highlights the potential of ferroptosis as a novel anticancer strategy ( Hassannia et al, 2019 ). A previous study reported that upregulation of glutathione peroxidase 4 (GPX4), a key negative regulator of ferroptosis, and downregulation of heme oxygenase-1 (HMOX1), which promotes ferroptosis by increasing the labile iron pool (LIP), were poor prognostic factors in ESCC ( Shishido et al, 2020 ). 5-Aminolevulinic acid (5-ALA) induces ferroptosis by modulating GPX4 and HMOX1 in ESCC ( Shishido et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…A previous study reported that upregulation of glutathione peroxidase 4 (GPX4), a key negative regulator of ferroptosis, and downregulation of heme oxygenase-1 (HMOX1), which promotes ferroptosis by increasing the labile iron pool (LIP), were poor prognostic factors in ESCC ( Shishido et al, 2020 ). 5-Aminolevulinic acid (5-ALA) induces ferroptosis by modulating GPX4 and HMOX1 in ESCC ( Shishido et al, 2020 ). Recently, several studies have revealed the predictive value of ferroptosis-related gene (FRG) signatures in various cancers ( Liang et al, 2020 ; Luo and Ma, 2021 ; Zheng et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Development and Validation of a Ferroptosis-Related Gene Signature and Nomogram for Predicting the Prognosis of Esophageal Squamous Cell Carcinoma

Cai

et al. 2021

Front. Genet.

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Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor with high mortality and poor prognosis. Ferroptosis is a newly discovered form of cell death induced by iron-catalyzed excessive peroxidation of polyunsaturated fatty acids (PUFAs). However, the prognostic value of ferroptosis-related genes (FRGs) for ESCC remains unclear. Based on the ESCC dataset from the Gene Expression Omnibus (GEO) database, we identified 39 prognostic FRGs through univariate Cox regression analysis. After LASSO regression and multivariate Cox regression analyses, a multigene signature based on 10 prognostic FRGs was constructed and successfully divided ESCC patients into two risk groups. Patients in the low-risk group showed a significantly better prognosis than patients in the high-risk group. In addition, we combined the risk score with clinical predictors to construct a nomogram for ESCC. The predictive ability of the nomogram was further verified by ROC curves and calibration plots in both the training and validation sets. The predictive power of the nomogram was demonstrated to be better than that of either the risk score or clinical variable alone. Furthermore, functional analysis revealed that the 10-FRG signature was mainly associated with ferroptosis, differentiation and immune response. Connectivity map analysis identified potential compounds capable of targeting FRGs in ESCC. Finally, we demonstrated the prognostic value of SRC gene in ESCC using the clinical samples and found that SRC inhibition sensitized ESCC cells to ferroptosis inducers by in vitro experiments. In conclusion, we identified and verified a 10-FRG prognostic signature and a nomogram, which provide individualized prognosis prediction and provide insight into potential therapeutic targets for ESCC.

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BACH1 promotes intervertebral disc degeneration by regulating HMOX1/GPX4 to mediate oxidative stress, ferroptosis, and lipid metabolism in nucleus pulposus cells

Yao

Cai

Wan

et al. 2023

The Journal of Gene Medicine

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Background: Intervertebral disc degeneration (IDD) is a primary health problem worldwide that involves oxidative stress, ferroptosis, and lipid metabolism. However, the underlying mechanism remains unclear. We investigated whether the transcription factor BTB and CNC homology 1 (BACH1) affected IDD progression by regulating HMOX1/GPX4-mediated ferroptosis and lipid metabolism in nucleus pulposus cells (NPCs).Methods: A rat IDD model was created to detect BACH1 expression in intervertebral disc tissues. Next, rat NPCs were isolated and treated with tert-butyl hydroperoxide (TBHP). BACH1, HMOX1, and GPX4 were knocked down, and oxidative stress and ferroptosis-related marker levels were examined. The binding of BACH1 to HMOX1 and of BACH1 to GPX4 was verified using chromatin immunoprecipitation (ChIP).Finally, untargeted lipid metabolism analysis was performed.Results: An IDD model was successfully created, and BACH1 activity was found to be enhanced in the rat IDD tissues. BACH1 inhibited TBHP-induced oxidative stress and oxidative stress-induced ferroptosis in NPCs. Simultaneously, ChIP verified that BACH1 protein bound to HMOX1 and targeted the HMOX1 transcription inhibition to affect oxidative stress in NPCs. ChIP also verified that BACH1 bound to GPX4 and targeted the GPX4 inhibition to affect ferroptosis in NPCs. Finally, BACH1 inhibition in vivo improved IDD and affected lipid metabolism. Conclusions:The transcription factor BACH1 promoted IDD by regulating HMOX1/ GPX4 to mediate oxidative stress, ferroptosis, and lipid metabolism in NPCs.

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Antitumor Effect of 5-Aminolevulinic Acid Through Ferroptosis in Esophageal Squamous Cell Carcinoma

Cited by 34 publications

References 37 publications

Light-Activated Protoporphyrin IX-Based Polysilsesquioxane Nanoparticles Induce Ferroptosis in Melanoma Cells

Light-Activated Protoporphyrin IX-Based Polysilsesquioxane Nanoparticles Induce Ferroptosis in Melanoma Cells

Development and Validation of a Ferroptosis-Related Gene Signature and Nomogram for Predicting the Prognosis of Esophageal Squamous Cell Carcinoma

BACH1 promotes intervertebral disc degeneration by regulating HMOX1/GPX4 to mediate oxidative stress, ferroptosis, and lipid metabolism in nucleus pulposus cells

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