Tumoral Malignancy Decreases Coupled with Higher ROS and Lipid Peroxidation in HCT116 Colon Cancer Cells upon Loss of PRDX6 DOI Creative Commons

Daniel J. Lagal,

Antonio M. Montes-Osuna,

Alberto Ortiz-Olivencia

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(7), P. 881 - 881

Published: July 22, 2024

Peroxiredoxin 6 (PRDX6) is an atypical member of the peroxiredoxin family that presents not only peroxidase but also phospholipase A2 and lysophosphatidylcholine acyl transferase activities able to act on lipid hydroperoxides cell membranes. It has been associated with proliferation invasive capacity different tumoral cells including colorectal cancer cells, although effect its removal in these yet studied. Here, using CRISPR/Cas9 technology, we constructed HCT116 line knockout for PRDX6 study whether mechanisms described other terms proliferation, migration, invasiveness apply this line. lacking showed increased ROS peroxidation, a decrease antioxidant response regulator NRF2, mitochondrial dysfunction, sensitivity ferroptosis. All alterations lead cells. Furthermore, reduced migratory consistent observed cadherin switch pro-invasive proteins such as MMPs. Therefore, mechanism behind effects loss could differ from HepG2 which coherent fact correlation expression patient survival hepatocellular carcinomas. Nonetheless, our results point protein good therapeutic target cancer.

Language: Английский

Cancer-associated fibroblasts reprogram cysteine metabolism to increase tumor resistance to ferroptosis in pancreatic cancer DOI Creative Commons
Yuchao Zhu, Shuai Fang, Bolin Fan

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(4), P. 1683 - 1700

Published: Jan. 1, 2024

Background: Pancreatic ductal adenocarcinoma (PDAC) is an insidious, rapidly progressing malignancy of the gastrointestinal tract.Due to its dense fibrous stroma and complex tumor microenvironment, neither which sensitive radiotherapy, pancreatic one malignancies with poorest prognosis.Therefore, detailed elucidation inhibitory microenvironment PDAC essential for development novel therapeutic strategies.Methods: We analyzed association between cancer-associated fibroblasts (CAFs) resistance ferroptosis in using conditioned CAF medium co-culture cancer cells.Abnormal cysteine metabolism was observed CAFs non-targeted metabolomics analysis liquid chromatography-tandem mass spectrometry (LC-MS/MS).The regulatory effects were investigated cells through measurement cell cloning, death, function, EdU assays.The exogenous intake examined a mouse xenograft model pathway on by western blotting, glutathione reactive oxygen species levels, among others.Results: It found that played critical role secreting cysteine, could increase ferroptosis.A previously unrecognized function sulfur transfer identified, increased extracellular supply support synthesis thus inducing resistance.Cysteine secretion be mediated TGF-β/SMAD3/ATF4 signaling axis. Conclusion:Taken together, findings demonstrate metabolic relationship cells, generated acts as substrate prevention oxidative damage suggests new targets PDAC.

Language: Английский

Citations

13
The Cancer Antioxidant Regulation System in Therapeutic Resistance DOI Creative Commons

Xuanhao Gu,

Chunyang Mu,

Rujia Zheng

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(7), P. 778 - 778

Published: June 27, 2024

Antioxidants play a pivotal role in neutralizing reactive oxygen species (ROS), which are known to induce oxidative stress. In the context of cancer development, cells adeptly maintain elevated levels both ROS and antioxidants through process termed "redox reprogramming". This balance optimizes proliferative influence while simultaneously reducing potential for cause damage cell. some cases, adapted antioxidant machinery can hamper efficacy treatments neoplastic diseases, representing significant facet resistance mechanisms observed therapy. this review, we outline contribution systems therapeutic resistance. We detail fundamental constituents these systems, encompassing central regulatory involving transcription factors (of particular importance is KEAP1/NRF2 signaling axis), molecular effectors antioxidants, auxiliary responsible NADPH generation. Furthermore, present recent clinical trials based on targeted treatment cancer, assessing as well challenges strategy Additionally, summarize pressing issues field, with aim illuminating path toward emergence novel anticancer approaches by orchestrating redox signaling.

Language: Английский

Citations

11
PRDX6 Prevents NNMT Ubiquitination and Degradation as a Nonenzymatic Mechanism to Promote Ovarian Cancer Progression DOI Creative Commons

Xingyun Wu,

Li Luo, Mao Wang

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Abstract Cancer cells cope with oxidative stress for their proliferation and metastasis by equipping antioxidant systems, among which the enzymes peroxiredoxins (PRDXs) play crucial roles. However, whether PRDXs exhibit nonenzymatic functions remains unclear. Here, it is shown that 1‐cysteine PRDX (PRDX6) upregulates nicotinamide N ‐methyltransferase (NNMT) to promote growth of ovarian cancer cells, independently PRDX6's enzymatic activities. Mechanistically, PRDX6 interacts NNMT prevent its binding E3 ubiquitin ligase tripartite‐motif protein 56 (TRIM56), leading inhibition ubiquitination at lysine 23 210 suppression subsequent proteasomal degradation. In addition, PRDX6‐mediated upregulation activates mitogen‐activated kinase (MAPK) signaling, thereby promoting cells. Notably, overexpression associated higher levels in human tissues predictive poor prognosis patients. Overall, findings illustrate a critical oncogenic mechanism enzyme progression beyond mechanisms.

Language: Английский

Citations

1
Versatile Nanomaterials That Interfere with Ferroptosis in the Tumor Microenvironment DOI Creative Commons
Yurong Liu,

Yunheng Liu,

Xinting Li

et al.

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 2461 - 2473

Published: Feb. 1, 2025

Ferroptosis is a type of iron-dependent programmed cell death characterized by depletion glutathione. Although generally less harmful to normal cells, in tumor the high demand for iron ions provides conditions conducive ferroptosis. In this review, we provide an overview recent progress research on regulation ferroptosis summarizing and assessing current state, trends, applications nanomaterials cells. Given advantages terms targeting, safety, improved drug efficacy, reduced side effects, these materials are considered have potential therapeutic value modulating cells via different mechanisms. respect, describe methods modifying interfering with glutathione activity lipid peroxidation. The development that can be applied induce or inhibit anticipated new options treatment diverse range diseases.

Language: Английский

Citations

1
Dual role of PRDX1 in redox-regulation and tumorigenesis: Past and future DOI
Xin–Yuan Guan, Yiyin Ruan, Xiaoxia Che

et al.

Free Radical Biology and Medicine, Journal Year: 2023, Volume and Issue: 210, P. 120 - 129

Published: Nov. 16, 2023

Language: Английский

Citations

19
Mitochondrial Physiology of Cellular Redox Regulations DOI Creative Commons
Petr Ježek, Andrea Dlasková, Hana Engstová

et al.

Physiological Research, Journal Year: 2024, Volume and Issue: Suppl 1, P. S217 - S242

Published: Aug. 27, 2024

Mitochondria (mt) represent the vital hub of molecular physiology cell, being decision-makers in cell life/death and information signaling, including major redox regulations signaling. Now we review recent advances understanding mitochondrial homeostasis, superoxide sources H2O2 consumers, i.e., antioxidant mechanisms, as well exemplar situations physiological intramitochondrial one mt-to-cytosol signals, which may be classified acute long-term signals. This exemplifies signals hypoxic adaptation upon insulin secretion pancreatic beta-cells. We also show how metabolic changes under these circumstances are linked to cristae narrowing at higher intensity ATP synthesis. Also, will discuss buffers, namely peroxiredoxin system, promote point out that pathological thresholds exist, specific for each type, above exceed regular capacity concomitant harmful processes oxidative stress subsequently initiate etiology numerous diseases. The signaling impaired when sunk such excessive pro-oxidative state.

Language: Английский

Citations

6
HJURP inhibits sensitivity to ferroptosis inducers in prostate cancer cells by enhancing the peroxidase activity of PRDX1 DOI Creative Commons
Wenjie Lai, Weian Zhu, Jianjie Wu

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 77, P. 103392 - 103392

Published: Oct. 10, 2024

Ferroptosis induction has emerged as a promising therapeutic approach for prostate cancer (PCa), either monotherapy or in combination with hormone therapy. Therefore, identifying the mechanisms regulating ferroptosis PCa cells is essential. Our previous study demonstrated that HJURP, an oncogene upregulated cells, plays role tumor proliferation. Here, we expand these findings by elucidating novel mechanism which HJURP inhibits sensitivity to inducers via PRDX1/reactive oxygen species (ROS) pathway vitro and vivo. Mechanistically, forms disulfide-linked intermediates PRDX1 through Cys

Language: Английский

Citations

5
Discovery of Urea Derivatives of Celastrol as Selective Peroxiredoxin 1 Inhibitors against Colorectal Cancer Cells DOI
Yang Li,

Yuyuan Zhu,

Fan-Fan Shang

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(9), P. 7176 - 7196

Published: April 29, 2024

Peroxiredoxin (PRDX1) is a tumor-overexpressed antioxidant enzyme for eliminating excessive reactive oxygen species (ROS) to protect tumor cells from oxidative damage. Herein, series of celastrol urea derivatives were developed based on its cocrystal structure with PRDX1, the aim pursuing PRDX1-specific inhibitor. Among them, derivative

Language: Английский

Citations

4
Seliciclib alleviates ulcerative colitis by inhibiting ferroptosis and improving intestinal inflammation DOI

Song Ya,

Qian Song,

Fangyan Tan

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 351, P. 122794 - 122794

Published: June 10, 2024

Language: Английский

Citations

4
CXCL8 Promotes Endothelial-to-Mesenchymal Transition of Endothelial Cells and Protects Cells from Erastin-Induced Ferroptosis via CXCR2-Mediated Activation of the NF-κB Signaling Pathway DOI Creative Commons
Haizhou Ji, Li Chen,

Mi Ren

et al.

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(9), P. 1210 - 1210

Published: Aug. 25, 2023

CXCL8-CXCR1/CXCR2 signaling pathways might form complex crosstalk among different cell types within the ovarian tumor microenvironment, thereby modulating behaviors of cells. This study aimed to investigate expression pattern CXCL8 in microenvironment and its impact on both endothelial-to-mesenchymal transition (EndMT) ferroptosis endothelial The human monocytic line THP-1 umbilical vein PUMC-HUVEC-T1 were used conduct vitro studies. Erastin was induce ferroptosis. Results showed that tumor-associated macrophages are major source microenvironment. treatment promoted nucleus entrance NF-κB p65 phosphorylation via CXCR2 cells, suggesting activated signaling. Via pathway, enhanced TGF-β1-induced EndMT cells elevated their SLC7A11 GPX4. These trends drastically weakened groups with knockdown or SB225002 treatment. TPCA-1 reversed CXCL8-induced upregulation protected from erastin-induced However, these protective effects largely canceled when knocked down. In summary, can activate pathway a CXCR2-dependent manner. CXCL8-CXCR2/NF-κB axis enhance GPX4 expression, protecting

Language: Английский

Citations

10