scholarly journals Opportunities for Ferroptosis in Cancer Therapy

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 986
Author(s):  
Kenji M. Fujihara ◽  
Bonnie Z. Zhang ◽  
Nicholas J. Clemons
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Therapeutic Strategy ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Cancer Therapeutics ◽  
Therapeutic Window ◽  
Anti Cancer

A critical hallmark of cancer cells is their ability to evade programmed apoptotic cell death. Consequently, resistance to anti-cancer therapeutics is a hurdle often observed in the clinic. Ferroptosis, a non-apoptotic form of cell death distinguished by toxic lipid peroxidation and iron accumulation, has garnered substantial attention as an alternative therapeutic strategy to selectively destroy tumours. Although there is a plethora of research outlining the molecular mechanisms of ferroptosis, these findings are yet to be translated into clinical compounds inducing ferroptosis. In this perspective, we elaborate on how ferroptosis can be leveraged in the clinic. We discuss a therapeutic window for compounds inducing ferroptosis, the subset of tumour types that are most sensitive to ferroptosis, conventional therapeutics that induce ferroptosis, and potential strategies for lowering the threshold for ferroptosis.

scholarly journals The MUDENG Augmentation: A Genesis in Anti-Cancer Therapy?

2020 ◽  
Vol 21 (15) ◽  
pp. 5583
Author(s):  
Manikandan Muthu ◽  
Sechul Chun ◽  
Judy Gopal ◽  
Gyun-Seok Park ◽  
Arti Nile ◽  
...  
Keyword(s):  
Cancer Research ◽  
Cell Death ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Tumor Necrosis ◽  
Cancer Therapeutics ◽  
Future Perspective ◽  
Normal Cells ◽  
Anti Cancer ◽  
Necrosis Factor

Despite multitudes of reports on cancer remedies available, we are far from being able to declare that we have arrived at that defining anti-cancer therapy. In recent decades, researchers have been looking into the possibility of enhancing cell death-related signaling pathways in cancer cells using pro-apoptotic proteins. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Mu-2/AP1M2 domain containing, death-inducing (MUDENG, MuD) have been established for their ability to bring about cell death specifically in cancer cells. Targeted cell death is a very attractive term when it comes to cancer, since most therapies also affect normal cells. In this direction TRAIL has made noteworthy progress. This review briefly sums up what has been done using TRAIL in cancer therapeutics. The importance of MuD and what has been achieved thus far through MuD and the need to widen and concentrate on applicational aspects of MuD has been highlighted. This has been suggested as the future perspective of MuD towards prospective progress in cancer research.

scholarly journals Iron toxicity, lipid peroxidation and ferroptosis after intracerebral haemorrhage

2019 ◽  
Vol 4 (2) ◽  
pp. 93-95 ◽  
Author(s):  
Jieru Wan ◽  
Honglei Ren ◽  
Jian Wang
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Intracerebral Haemorrhage ◽  
Neuronal Death ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Iron Toxicity ◽  
Secondary Brain Injury

Intracerebral haemorrhage (ICH) is a devastating type of stroke with high mortality and morbidity. However, we have few options for ICH therapy and limited knowledge about post-ICH neuronal death and related mechanisms. In the aftermath of ICH, iron overload within the perihaematomal region can induce lethal reactive oxygen species (ROS) production and lipid peroxidation, which contribute to secondary brain injury. Indeed, iron chelation therapy has shown efficacy in preclinical ICH studies. Recently, an iron-dependent form of non-apoptotic cell death known as ferroptosis was identified. It is characterised by an accumulation of iron-induced lipid ROS, which leads to intracellular oxidative stress. The ROS cause damage to nucleic acids, proteins and lipid membranes, and eventually cell death. Recently, we and others discovered that ferroptosis does occur after haemorrhagic stroke in vitro and in vivo and contributes to neuronal death. Inhibition of ferroptosis is beneficial in several in vivo and in vitro ICH conditions. This minireview summarises current research on iron toxicity, lipid peroxidation and ferroptosis in the pathomechanisms of ICH, the underlying molecular mechanisms of ferroptosis and the potential for combined therapeutic strategies. Understanding the role of ferroptosis after ICH will provide a vital foundation for cell death-based ICH treatment and prevention.

scholarly journals Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Victoria D. Turubanova ◽  
Tatiana A. Mishchenko ◽  
Irina V. Balalaeva ◽  
Iuliia Efimova ◽  
Nina N. Peskova ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Adaptive Immune System ◽  
Immunogenic Cell Death ◽  
Immunodeficient Mice ◽  
Anti Cancer ◽  
Molecular Patterns

AbstractThe immunogenicity of dying cancer cells determines the efficacy of anti-cancer therapy. Photodynamic therapy (PDT) can induce immunogenic cell death (ICD), which is characterized by the emission of damage-associated molecular patterns (DAMPs) from dying cells. This emission can trigger effective anti-tumor immunity. Only a few photosensitizers are known to induce ICD and, therefore, there is a need for development of new photosensitizers that can induce ICD. The purpose of this work was to analyze whether photosensitizers developed in-house from porphyrazines (pz I and pz III) can induce ICD in vitro and in vivo when used in PDT. We indetified the optimal concentrations of the photosensitizers and found that, at a light dose of 20 J/cm2 (λex 615–635 nm), both pz I and pz III efficiently induced cell death in cancer cells. We demonstrate that pz I localized predominantly in the Golgi apparatus and lysosomes while pz III in the endoplasmic reticulum and lysosomes. The cell death induced by pz I-PDT was inhibited by zVAD-fmk (apoptosis inhibitor) but not by ferrostatin-1 and DFO (ferroptosis inhibitors) or by necrostatin-1 s (necroptosis inhibitor). By contrast, the cell death induced by pz III-PDT was inhibited by z-VAD-fmk and by the necroptosis inhibitor, necrostatin-1 s. Cancer cells induced by pz I-PDT or pz III-PDT released HMGB1 and ATP and were engulfed by bone marrow-derived dendritic cells, which then matured and became activated in vitro. We demonstrate that cancer cells, after induction of cell death by pz I-PDT or pz III-PDT, are protective when used in the mouse model of prophylactic tumor vaccination. By vaccinating immunodeficient mice, we prove the role of the adaptive immune system in protecting against tumours. All together, we have shown that two novel porphyrazines developed in-house are potent ICD inducers that could be effectively applied in PDT of cancer.

scholarly journals Caspase-Independent Regulated Necrosis Pathways as Potential Targets in Cancer Management

2021 ◽  
Vol 10 ◽  
Author(s):  
Jianyao Lou ◽  
Yunxiang Zhou ◽  
Zengyu Feng ◽  
Mindi Ma ◽  
Yihan Yao ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Multiple Modes ◽  
Cancer Management ◽  
Regulated Necrosis ◽  
Anti Cancer ◽  
Cancer Initiation

Regulated necrosis is an emerging type of cell death independent of caspase. Recently, with increasing findings of regulated necrosis in the field of biochemistry and genetics, the underlying molecular mechanisms and signaling pathways of regulated necrosis are gradually understood. Nowadays, there are several modes of regulated necrosis that are tightly related to cancer initiation and development, including necroptosis, ferroptosis, parthanatos, pyroptosis, and so on. What’s more, accumulating evidence shows that various compounds can exhibit the anti-cancer effect via inducing regulated necrosis in cancer cells, which indicates that caspase-independent regulated necrosis pathways are potential targets in cancer management. In this review, we expand the molecular mechanisms as well as signaling pathways of multiple modes of regulated necrosis. We also elaborate on the roles they play in tumorigenesis and discuss how each of the regulated necrosis pathways could be therapeutically targeted.

scholarly journals Identification of anticancer activity of phytoconstituents from mangrove

2019 ◽  
Vol 10 (2) ◽  
pp. 791-794
Author(s):  
Sheela Devi A ◽  
Joseph J ◽  
Bhuvaneshwari V
Keyword(s):  
Cell Death ◽  
Medicinal Plants ◽  
Anticancer Activity ◽  
Therapeutic Strategy ◽  
Apoptotic Cell ◽  
Marine Ecosystem ◽  
Apoptotic Cell Death ◽  
Traditional System ◽  
Anti Cancer ◽  
Effective Therapeutic Strategy

Medicinal plants from the marine ecosystem are a rich source of medicinal plants having a potential for miracle drugs. It is clear from the observation that the local inhabitants of Pichavaram mangrove forest have excellent knowledge about the phytomedicine. Thus they have developed their traditional system of utilizing these mangroves for medicinal purposes. Cancer is the name given to a collection of related and multistep disease. In all types of cancer, a few of the body's cells begin to divide without stopping and spread into the surrounding. It is developed by environmental, physical, chemical, metabolic and genetic factors. In this study, methanol was used to prepare an extract from A. marina leaves and screened for anticancer activity. The phytoconstituents like alkaloids, flavonoids, saponin and tannin present in the extract were quantified, and anticancer activity of the same was identified. Further, the apoptotic cell death effect of methanol extract on the Hela cell line was determined. The flavonoids of A. marina showed higher anti-cancer activity on Hela cells followed by tannin, alkaloids and saponin. The result of the apoptotic cell death effect of A. marina may provide an effective therapeutic strategy against cervical cancer. Finally, it is concluded that the extract of A. marina exhibited anticancer activity.

scholarly journals Ferroptosis: The Silver Lining of Cancer Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhengming Tang ◽  
Zhijie Huang ◽  
Yisheng Huang ◽  
Yuanxin Chen ◽  
Mingshu Huang ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Future Perspectives ◽  
Major Focus ◽  
Therapeutic Modalities ◽  
Regulated Cell Death ◽  
Physiological Properties ◽  
Silver Lining

Regulatory cell death has been a major focus area of cancer therapy research to improve conventional clinical cancer treatment (e.g. chemotherapy and radiotherapy). Ferroptosis, a novel form of regulated cell death mediated by iron-dependent lipid peroxidation, has been receiving increasing attention since its discovery in 2012. Owing to the highly iron-dependent physiological properties of cancer cells, targeting ferroptosis is a promising approach in cancer therapy. In this review, we summarised the characteristics of ferroptotic cells, associated mechanisms of ferroptosis occurrence and regulation and application of the ferroptotic pathway in cancer therapy, including the use of ferroptosis in combination with other therapeutic modalities. In addition, we presented the challenges of using ferroptosis in cancer therapy and future perspectives that may provide a basis for further research.

scholarly journals Combination of Arsenic Trioxide and Valproic Acid Efficiently Inhibits Growth of Lung Cancer Cells via G2/M-Phase Arrest and Apoptotic Cell Death

2020 ◽  
Vol 21 (7) ◽  
pp. 2649
Author(s):  
Hyun Kyung Park ◽  
Bo Ram Han ◽  
Woo Hyun Park
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Lung Cancer Cells ◽  
Phase Arrest ◽  
Anti Cancer ◽  
M Phase

Arsenic trioxide (ATO; As2O3) has anti-cancer effects in various solid tumors as well as hematological malignancy. Valproic acid (VPA), which is known to be a histone deacetylase inhibitor, has also anti-cancer properties in several cancer cells including lung cancer cells. Combined treatment of ATO and VPA (ATO/VPA) could synergistically enhance anti-cancer effects and reduce ATO toxicity ATO. In this study, the combined anti-cancer effects of ATO and VPA (ATO/VPA) was investigated in NCI-H460 and NCI-H1299 lung cancer cells in vitro and in vivo. A combination of 3 μM ATO and 3 mM VPA (ATO/VPA) strongly inhibited the growths of both lung cancer cell types. DNA flow cytometry indicated that ATO/VPA significantly induced G2/M-phase arrest in both cell lines. In addition, ATO/VPA strongly increased the percentages of sub-G1 cells and annexin V-FITC positive cells in both cells. However, lactate dehydrogenase (LDH) release from cells was not increased in ATO/VPA-treated cells. In addition, ATO/VPA increased apoptosis in both cell types, accompanied by loss of mitochondrial membrane potential (MMP, ∆Ψm), activation of caspases, and cleavage of anti-poly ADP ribose polymerase-1. Moreover, a pan-caspase inhibitor, Z-VAD, significantly reduced apoptotic cell death induced by ATO/VPA. In the xenograft model, ATO/VPA synergistically inhibited growth of NCI-H460-derived xenograft tumors. In conclusion, the combination of ATO/VPA effectively inhibited the growth of lung cancer cells through G2/M-phase arrest and apoptotic cell death, and had a synergistic antitumor effect in vivo.

scholarly journals Mutagenic Consequences of Sublethal Cell Death Signaling

2021 ◽  
Vol 22 (11) ◽  
pp. 6144
Author(s):  
Christine J. Hawkins ◽  
Mark A. Miles
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Oncogenic Potential ◽  
Genomic Changes ◽  
Cell Death Pathways ◽  
Anti Cancer ◽  
Cell Death Signaling ◽  
Mechanisms Of Mutagenesis

Many human cancers exhibit defects in key DNA damage response elements that can render tumors insensitive to the cell death-promoting properties of DNA-damaging therapies. Using agents that directly induce apoptosis by targeting apoptotic components, rather than relying on DNA damage to indirectly stimulate apoptosis of cancer cells, may overcome classical blocks exploited by cancer cells to evade apoptotic cell death. However, there is increasing evidence that cells surviving sublethal exposure to classical apoptotic signaling may recover with newly acquired genomic changes which may have oncogenic potential, and so could theoretically spur the development of subsequent cancers in cured patients. Encouragingly, cells surviving sublethal necroptotic signaling did not acquire mutations, suggesting that necroptosis-inducing anti-cancer drugs may be less likely to trigger therapy-related cancers. We are yet to develop effective direct inducers of other cell death pathways, and as such, data regarding the consequences of cells surviving sublethal stimulation of those pathways are still emerging. This review details the currently known mutagenic consequences of cells surviving different cell death signaling pathways, with implications for potential oncogenic transformation. Understanding the mechanisms of mutagenesis associated (or not) with various cell death pathways will guide us in the development of future therapeutics to minimize therapy-related side effects associated with DNA damage.

scholarly journals Apoptotic Cell Death Induction Through Pectin, Guar Gum and Zinc Oxide Nanocomposite in A549 Lung Adenocarcinomas

2021 ◽  
Vol 12 (2) ◽  
pp. 1856-1869
Keyword(s):  
Cell Death ◽  
Zinc Oxide ◽  
Cancer Cells ◽  
Guar Gum ◽  
Apoptotic Cell ◽  
Human Peripheral Blood ◽  
Reactive Oxygen Species Generation ◽  
A549 Cells ◽  
Target Cells ◽  
Anti Cancer

Previously, we reported the immunostimulatory potential of the nanocomposite prepared from biopolymers (Pectin and Guar gum) and zinc oxide (Pec-gg-ZnO) on human peripheral-blood lymphocytes leading to enhanced anti-cancer immunity. The current study aims to describe the direct anti-cancer potential of Pec-gg-ZnO nanocomposite and the relevant mechanism of cell death induction in human lung carcinomas (A549). The cytotoxicity assay revealed the anti-cancer potential of Pec-gg-ZnO nanocomposite towards A549 cells, cervical adenocarcinoma (HeLa), and prostatic small cell carcinoma (PC-3). The IC50 values were 83.67 ± 0.10 μg/ml, 87.25 ± 0.03 μg/ml and 85.95 ± 0.03 μg/ml for A549, HeLa and PC-3 cells, respectively. The nanocomposite's cancer cells' killing capabilities were significantly higher than pectin and guar gum alone. Hemolysis assay revealed that synthesized Pec-gg-ZnO nanocomposite is biocompatible at 2.5 mg/ml. S phase arrest with enhanced sub-G1 (apoptotic cells) population was examined in A549 cells treated with Pec-gg-ZnO nanocomposite. The nanocomposite caused apoptosis of target cells by inducing mitochondrial depolarisation, reactive oxygen species generation, caspase-3 and Poly (ADP-ribose) polymerase 1 (PARP1) activation resulting in DNA fragmentation. Collectively, the current data revealed that Pec-gg-ZnO nanocomposite is a novel polymer-based anti-cancer agent capable of inducing apoptotic pathways in cancer cells.

Sign in / Sign up

Export Citation Format

Share Document