Ferroptosis, necroptosis, and pyroptosis in anticancer immunity

Journal of Hematology & Oncology, Год журнала: 2020, Номер 13(1)

Опубликована: Авг. 10, 2020

Abstract In recent years, cancer immunotherapy based on immune checkpoint inhibitors (ICIs) has achieved considerable success in the clinic. However, ICIs are significantly limited by fact that only one third of patients with most types respond to these agents. The induction cell death mechanisms other than apoptosis gradually emerged as a new treatment strategy because tumors harbor innate resistance apoptosis. date, possibility combining two modalities not been discussed systematically. Recently, few studies revealed crosstalk between distinct and antitumor immunity. pyroptosis, ferroptosis, necroptosis combined showed synergistically enhanced activity, even ICI-resistant tumors. Immunotherapy-activated CD8+ T cells traditionally believed induce tumor via following main pathways: (i) perforin-granzyme (ii) Fas-FasL. identified mechanism which suppress growth inducing ferroptosis provoked review relationship system activation. Hence, this review, we summarize knowledge reciprocal interaction immunity mechanisms, particularly necroptosis, three potentially novel immunogenic death. Because evidence is derived from using animal models, also reviewed related bioinformatics data available for human tissues public databases, partially confirmed presence interactions activation

Язык: Английский

---

Ferroptosis in cancer and cancer immunotherapy

Cancer Communications, Год журнала: 2022, Номер 42(2), С. 88 - 116

Опубликована: Фев. 1, 2022

Abstract The hallmark of tumorigenesis is the successful circumvention cell death regulation for achieving unlimited replication and immortality. Ferroptosis a newly identified type dependent on lipid peroxidation which differs from classical programmed in terms morphology, physiology biochemistry. broad spectrum injury tumor tolerance are main reasons radiotherapy chemotherapy failure. effective rate immunotherapy as new treatment method less than 30%. can be seen radiotherapy, chemotherapy, immunotherapy; therefore, ferroptosis activation may potential strategy to overcome drug resistance mechanism traditional cancer treatments. In this review, characteristics causes by briefly described. addition, three metabolic regulations its crosstalk with signaling pathways summarized. Collectively, these findings suggest vital role based interaction immunotherapy, thus, indicating remarkable treatment.

Язык: Английский

---

Ferroptosis and Cancer: Mitochondria Meet the “Iron Maiden” Cell Death

Cells, Год журнала: 2020, Номер 9(6), С. 1505 - 1505

Опубликована: Июнь 20, 2020

Ferroptosis is a new type of oxidative regulated cell death (RCD) driven by iron-dependent lipid peroxidation. As major sites iron utilization and master regulators metabolism, mitochondria are the main source reactive oxygen species (ROS) and, thus, play role in this RCD. is, indeed, associated with severe damage mitochondrial morphology, bioenergetics, metabolism. Furthermore, dysregulation metabolism considered biochemical feature neurodegenerative diseases linked to ferroptosis. Whether dysfunction can, per se, initiate ferroptosis whether function context-dependent still under debate. Cancer cells accumulate high levels ROS promote their metabolic activity growth. Of note, cancer rewiring often acquired sensitivity This strongly suggests that may act as an adaptive response imbalance constitute promising way eradicate malignant cells. Here, we review current literature on ferroptosis, discuss opportunities potentially use mitochondria-mediated strategy for therapy.

Язык: Английский

---

Inhibition of ferroptosis alleviates atherosclerosis through attenuating lipid peroxidation and endothelial dysfunction in mouse aortic endothelial cell

Free Radical Biology and Medicine, Год журнала: 2020, Номер 160, С. 92 - 102

Опубликована: Авг. 5, 2020

Язык: Английский

---

Lipid composition of the cancer cell membrane

Journal of Bioenergetics and Biomembranes, Год журнала: 2020, Номер 52(5), С. 321 - 342

Опубликована: Июль 26, 2020

Abstract Cancer cell possesses numerous adaptations to resist the immune system response and chemotherapy. One of most significant properties neoplastic cells is altered lipid metabolism, consequently, abnormal membrane composition. Like in case phosphatidylcholine, these changes result modulation certain enzymes accumulation energetic material, which could be used for a higher proliferation rate. The are so prominent, that some lipids, such as phosphatidylserines, even considered cancer biomarkers. Additionally, biophysical membranes lead resistance chemotherapy, finally disturbances signalling pathways. Namely, increased levels like instance phosphatidylserine, attenuation response. Also, saturation prevent from demanding conditions microenvironment. Particularly interesting significance cholesterol content metastasis. This review paper discusses roles each type physiology. combined theoretical data with clinical studies show novel therapeutic options concerning oncology.

Язык: Английский

---

Identification of a small molecule as inducer of ferroptosis and apoptosis through ubiquitination of GPX4 in triple negative breast cancer cells

Journal of Hematology & Oncology, Год журнала: 2021, Номер 14(1)

Опубликована: Янв. 20, 2021

Abstract Background TNBC is the most aggressive breast cancer with higher recurrence and mortality rate than other types of cancer. There an urgent need for identification therapeutic agents unique mode action overcoming current challenges in treatment. Methods Different inhibitors were used to study cell death manner DMOCPTL . RNA silencing was evaluate functions GPX4 ferroptosis apoptosis cells EGR1 apoptosis. Immunohistochemical assay tissue microarray investigating correlation TNBC. Computer-aided docking small molecule probe binding GPX4. Results , a derivative natural product parthenolide, exhibited about 15-fold improvement comparing that parent compound PTL cells. The showed anti-TNBC effect mainly by inducing through ubiquitination indicated induced directly protein. To best our knowledge, this first report Moreover, mechanism regulation still obscure. Here, we firstly reveal regulated mitochondria-mediated Compound 13 prodrug effectively inhibited growth tumor prolonged lifespan mice vivo, no obvious toxicity observed. Conclusions These findings revealed novel induce provided up-regulation deserves further studies as lead ultimate discovery effective drug.

Язык: Английский

---

Enhanced Ferroptosis by Oxygen-Boosted Phototherapy Based on a 2-in-1 Nanoplatform of Ferrous Hemoglobin for Tumor Synergistic Therapy

ACS Nano, Год журнала: 2020, Номер 14(3), С. 3414 - 3425

Опубликована: Март 10, 2020

Photodynamic therapy (PDT) combined with oxygenating strategies is widely employed in cancer treatment; however, oxygen-boosted PDT has failed to achieve an ideal effect due the complexity, heterogeneity, and irreversible hypoxic environment generated by tumor tissues. With emergence of Fe-dependent ferroptosis boasting reactive oxygen species (ROS) cytotoxicity as well, such a chemodynamic approach drawn extensive attention. In this study, hemoglobin (Hb) connected photosensitizer chlorin e6 (Ce6) construct 2-in-1 nanoplatform (SRF@Hb-Ce6) Sorafenib (SRF, promotor) loaded, combining potent ferroptosis. Benefiting from intrinsic presence Fe capable binding oxygen, concurrently furnishes for oxygen-dependent Furthermore, amphiphilic MMP2-responsive peptide incorporated into skeleton ensure drug-release specificity safety improvement. Correlative measurements demonstrate potentiation SRF@Hb-Ce6. More importantly, strengthens recruiting immune cells secrete IFN-γ, which can sensitize our findings. The therapeutic synergistic treatment SRF@Hb-Ce6 vitro vivo was proven significant, revealing promising prospects nanoplatform.

Язык: Английский

---

GPX4: The hub of lipid oxidation, ferroptosis, disease and treatment

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2023, Номер 1878(3), С. 188890 - 188890

Опубликована: Март 29, 2023

Язык: Английский

---

Ferroptosis Inducers Are a Novel Therapeutic Approach for Advanced Prostate Cancer

Cancer Research, Год журнала: 2021, Номер 81(6), С. 1583 - 1594

Опубликована: Янв. 22, 2021

Abstract Ferroptosis is a type of programmed cell death induced by the accumulation lipid peroxidation and reactive oxygen species in cells. It has been recently demonstrated that cancer cells are vulnerable to ferroptosis inducers (FIN). However, therapeutic potential FINs prostate preclinical settings not explored. In this study, we demonstrate mediators ferroptosis, solute carrier family 7 member 11, SLC3A2, glutathione peroxidase, expressed treatment-resistant cancer. We further sensitive two FINs, erastin RSL3. Treatment with RSL3 led significant decrease growth migration vitro significantly delayed tumor vivo, no measurable side effects. Combination or standard-of-care second-generation antiandrogens for advanced halted vivo. These results independently combination as novel strategies Significance: findings reveal induction new strategy monotherapy antiandrogens.

Язык: Английский

---

The emerging role of ferroptosis in intestinal disease

Cell Death and Disease, Год журнала: 2021, Номер 12(4)

Опубликована: Март 17, 2021

Ferroptosis is a newly recognised type of regulated cell death (RCD) characterised by iron-dependent accumulation lipid peroxidation. It significantly distinct from other RCDs at the morphological, biochemical, and genetic levels. Recent reports have implicated ferroptosis in multiple diseases, including neurological disorders, kidney injury, liver cancer. Ferroptotic has also been associated with dysfunction intestinal epithelium, which contributes to several diseases. Research on may provide new understanding disease pathogenesis that benefits clinical treatment. In this review, we an overview its underlying mechanisms, then describe emerging role ischaemia/reperfusion (I/R) inflammatory bowel (IBD), colorectal cancer (CRC).

Язык: Английский

---