Enhancement of ferroptosis by boric acid and its potential use as chemosensitizer in anticancer chemotherapy DOI
Alessandro Corti,

Silvia Dominici,

Simona Piaggi

et al.

BioFactors, Journal Year: 2022, Volume and Issue: 49(2), P. 405 - 414

Published: Dec. 5, 2022

Ferroptosis is a form of regulated cell death (RCD) characterized by intracellular iron ion accumulation and reactive oxygen species (ROS)-induced lipid peroxidation. in cancer ferroptosis-related anticancer drugs have recently gained interest the field treatment. Boron an essential trace element playing important role several biological processes. Recent studies described contrasting effects boric acid (BA) cells, ranging from protective/mitogenic to damaging/antiproliferative. Interestingly, boron has been shown interfere with critical factors involved ferroptosis-intracellular glutathione peroxidation first place. Thus, present study was aimed verify ability modulate ferroptotic process HepG2 model hepatocellular carcinoma. Our results indicate that-when used at high, pharmacological concentrations-BA can increase ROS, glutathione, TBARS levels, enhance ferroptosis induced RSL3 erastin. Also, high BA concentrations directly induce ferroptosis, such BA-induced add cytotoxic sorafenib, doxorubicin cisplatin. These observations suggest that could be exploited as chemo-sensitizer agent order overcome drug resistance selected conditions. However, possibility reaching suitably tumor microenvironment will need further investigated.

Language: Английский

Iron, Oxidative Stress, and Metabolic Dysfunction—Associated Steatotic Liver Disease DOI Creative Commons

Sophie Gensluckner,

Bernhard Wernly, Christian Datz

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(2), P. 208 - 208

Published: Feb. 7, 2024

Excess free iron is a substrate for the formation of reactive oxygen species (ROS), thereby augmenting oxidative stress. Oxidative stress well-established cause organ damage in liver, main site storage. Ferroptosis, an iron-dependent mechanism regulated cell death, has recently been gaining attention development and progression liver disease. We therefore summarize mechanisms metabolism, its close connection to ferroptosis, particular relevance disease metabolic-dysfunction-associated fatty potential targets therapy from clinical perspective.

Language: Английский

Citations

24
Ferroptosis: From regulation of lipid peroxidation to the treatment of diseases DOI
Yonghui Lv, Meiying Wu, Zhe Wang

et al.

Cell Biology and Toxicology, Journal Year: 2022, Volume and Issue: 39(3), P. 827 - 851

Published: Dec. 2, 2022

Language: Английский

Citations

49
Autophagy activation is required for N6-methyladenosine modification to regulate ferroptosis in hepatocellular carcinoma DOI Creative Commons
Yujia Li, Mei Guo,

Yangling Qiu

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 69, P. 102971 - 102971

Published: Dec. 1, 2023

Although ferroptosis holds promise as a new strategy for treating hepatocellular carcinoma (HCC), there are several obstacles that need to be overcome. One major challenge is the lack of understanding about mechanisms underlying ferroptosis. Additionally, while m6A modification has been shown regulate various forms cell death, its role in regulating HCC largely overlooked. Bridging this knowledge gap, our study aimed elucidate regulatory influence on Dot blot and EpiQuik RNA Methylation Quantitative kit detected changes overall level during HCC. MeRIP-qPCR RIP-qPCR identified ATG5 mRNA was significant changed. BALB/c nude mice were used construct xenograft tumor models verify phenotypes upon YTHDC2 silencing. In addition, patient-derived organoid demonstrate induction an effective against Our inducing promising combatting Specifically, we have found correlation between high levels Notably, discovered elevation mediated by WTAP dependent reading protein YTHDC2. Importantly, inhibition either or effectively prevented suppressed development both vitro vivo models. revealed upregulates expression post-transcriptionally m6A-YTHDC2-dependent manner, thereby promoting translation These findings implications innovative therapeutic approaches treatment.

Language: Английский

Citations

31
Saikosaponin A triggers cell ferroptosis in hepatocellular carcinoma by inducing endoplasmic reticulum stress-stimulated ATF3 expression DOI
Tian Lan, Wen Wang,

Xi-xi Zeng

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2023, Volume and Issue: 674, P. 10 - 18

Published: June 28, 2023

Language: Английский

Citations

29
Epigenetic and Post-Translational Modifications in Ferroptosis Regulation and Hepatocellular Carcinoma: New Frontiers in Therapeutic Targeting DOI

Soheil Bolandi,

Samaneh Dodge,

Zahra Zahed

et al.

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: unknown, P. 155991 - 155991

Published: April 1, 2025

Language: Английский

Citations

1
SHP-1/STAT3-Signaling-Axis-Regulated Coupling between BECN1 and SLC7A11 Contributes to Sorafenib-Induced Ferroptosis in Hepatocellular Carcinoma DOI Open Access
Chaoyuan Huang, Li‐Ju Chen, Grace Chen

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(19), P. 11092 - 11092

Published: Sept. 21, 2022

Ferroptosis is a type of iron-dependent cell death pertaining to an excess lipid peroxidation. It has been suggested that sorafenib-an anti-angiogenic medication for hepatocellular carcinoma (HCC)-induces ferroptosis, but the underlying mechanism this remains largely unknown. We employed siRNA-mediated gene silencing investigate role Src homology region 2 domain-containing phosphatase-1 (SHP-1), following sorafenib treatment, in cystine/glutamate-antiporter-system-Xc--regulated cystine uptake. Co-immunoprecipitation was also performed examine interactions between MCL1, beclin 1 (BECN1), and solute carrier family 7 member 11 (SLC7A11), which functions as catalytic subunit system Xc-. The results study showed enhanced activity SHP-1, dephosphorylated STAT3, downregulated expression MCL1 and, consequently, reduced association BECN1. In contrast, increased binding BECN1 SLC7A11 observed treatment. elevated interaction inhibited Xc-, whereas restored intake protected cells from ferroptosis. Notably, ectopic uncoupled rescued viability by attenuating revealed ferroptosis could be induced HCC via SHP-1/STAT3-mediated downregulation subsequent inhibition binding.

Language: Английский

Citations

35
Transferrin Receptor is Associated with Sensitivity to Ferroptosis Inducers in Hepatocellular Carcinoma DOI

Maki Hiromatsu,

Katsuya Toshida, Shinji Itoh

et al.

Annals of Surgical Oncology, Journal Year: 2023, Volume and Issue: 30(13), P. 8675 - 8689

Published: Aug. 7, 2023

Language: Английский

Citations

20
Iron as a therapeutic target in chronic liver disease DOI Creative Commons

Elias Kouroumalis,

Ioannis Tsomidis, Argyro Voumvouraki

et al.

World Journal of Gastroenterology, Journal Year: 2023, Volume and Issue: 29(4), P. 616 - 655

Published: Jan. 20, 2023

It was clearly realized more than 50 years ago that iron deposition in the liver may be a critical factor development and progression of disease. The recent clarification ferroptosis as specific form regulated hepatocyte death different from apoptosis description ferritinophagy variation autophagy prompted detailed investigations on association liver. In this review, we will present brief discussion absorption handling by with emphasis role macrophages significance regulators hepcidin, transferrin, ferritin homeostasis. regulation endogenous exogenous mod-ulators examined. Furthermore, involvement various diseases including alcoholic non-alcoholic disease, chronic hepatitis B C, fibrosis, hepatocellular carcinoma (HCC) analyzed. Finally, experimental clinical results following interventions to reduce promising manipulation presented. Most benefited inhibition using inhibitors notable exception HCC, where induction is desired effect. Current evidence mostly stems vitro vivo studies need for well-designed future trials warranted.

Language: Английский

Citations

18
Recent advancements in nanomaterial-mediated ferroptosis-induced cancer therapy: Importance of molecular dynamics and novel strategies DOI Creative Commons
Namdev Dhas, Ritu Kudarha, Ruchı Tıwarı

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 346, P. 122629 - 122629

Published: April 15, 2024

Ferroptosis is a novel type of controlled cell death resulting from an imbalance between oxidative harm and protective mechanisms, demonstrating significant potential in combating cancer. It differs other forms death, such as apoptosis necrosis. Molecular therapeutics have hard time playing the long-acting role ferroptosis induction due to their limited water solubility, low targeting capacity, quick metabolism vivo. To this end, small molecule inducers based on biological factors long been used strategy induce death. Research into advancements nanotechnology led discovery that nanomaterials are superior medications triggering ferroptosis. Nanomaterials derived iron can enhance by directly releasing large quantities increasing ROS levels. Moreover, utilizing promote programmed minimizes probability unfavorable effects induced mutations cancer-associated genes RAS TP53. Taken together, review summarizes molecular mechanisms involved along with classification induction. also emphasized importance organelles control cancer therapy. The trigger categorized explained. Iron-based noniron-based characterization at cellular levels explored, which will be useful for inducing leads reduced tumor growth. Within framework, we offer synopsis, traverses well-established mechanism offers practical suggestions design therapeutic use nanomaterials.

Language: Английский

Citations

8
Ferroptosis in Liver Disease: Natural Active Compounds and Therapeutic Implications DOI Creative Commons

Zhili Wu,

Yanru Zhu,

Wen‐Chao Liu

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(3), P. 352 - 352

Published: March 15, 2024

Ferroptosis is an emerging type of regulated cell death usually accompanied by the accumulation ferrous ions (Fe2+) and lipid peroxides. As metabolic hub body, liver crucial for iron storage metabolism. The seems to be closely related ferroptosis through Liver disease greatly threatens host health, exploring effective interventions essential. Mounting studies have demonstrated that one possible pathogenic mechanisms involved in disease. Targeting may provide a promising opportunity treating However, drugs targeting are extremely limited. Therefore, it urgent need develop new safe regulators. Natural active compounds (NAC), especially those derived from traditional Chinese medicine, recently shown great therapeutic potential via modulating ferroptosis-related genes or pathways. Here, we outline molecular mechanism systematically summarize regulatory function NAC on Finally, discuss application prospects problems concerning as regulators managing

Language: Английский

Citations

5