Ferroptosis: Potential opportunities for natural products in cancer therapy

Phytotherapy Research, Journal Year: 2023, Volume and Issue: 38(3), P. 1173 - 1190

Published: Dec. 20, 2023

Abstract Cancer cells often exhibit defects in the execution of cell death, resulting poor clinical outcomes for patients with many cancer types. Ferroptosis is a newly discovered form programmed death characterized by intracellular iron overload and lipid peroxidation membrane. Increasing evidence suggests that ferroptosis closely associated wide variety physiological pathological processes, particularly cancer. Notably, various bioactive natural products have been shown to induce initiation cells, thereby exerting anticancer effects. In this review, we summarize core regulatory mechanisms multifaceted roles Importantly, focus on regulate such as terpenoids, polyphenols, alkaloids, steroids, quinones, polysaccharides. The efficacy, adverse effects, drug–drug interactions these need be evaluated further high‐quality studies accelerate their application treatment.

Language: Английский

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MAPK14 as a key gene for regulating inflammatory response and macrophage M1 polarization induced by ferroptotic keratinocyte in psoriasis

Inflammation, Journal Year: 2024, Volume and Issue: 47(5), P. 1564 - 1584

Published: March 5, 2024

Language: Английский

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Antitumor activity of dictamnine against colorectal cancer through induction of ferroptosis and inhibition of M2 macrophage polarization via the MAPK signaling

Archives of Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: 758, P. 110051 - 110051

Published: June 6, 2024

Language: Английский

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Gestational exposure to 1-NP induces ferroptosis in placental trophoblasts via CYP1B1/ERK signaling pathway leading to fetal growth restriction

Chemico-Biological Interactions, Journal Year: 2023, Volume and Issue: 387, P. 110812 - 110812

Published: Nov. 20, 2023

Fetal growth restriction (FGR) is a prevalent complication in obstetrics, yet its exact aetiology remains unknown. Numerous studies suggest that the degradation of living environment significant risk factor for FGR. 1-Nitropyrene (1-NP) widespread environmental pollutant as representative substance nitro-polycyclic aromatic hydrocarbons. In this study, we revealed 1-NP induced FGR fetal mice by constructing exposed pregnant models. Intriguingly, found placental trophoblasts exhibited ferroptosis, which was similarly detected from human patients. regard, established cell model vitro using two trophoblast lines, HTR8/SVneo and JEG-3. We not only impaired proliferation, migration, invasion angiogenesis trophoblasts, but also severe cellular ferroptosis. Meanwhile, ferroptosis inhibitor ferrostatin-1 (Fer-1) effectively rescued 1-NP-induced biological function impairment. Mechanistically, regulated activating ERK signaling pathway. Moreover, innovatively CYP1B1 essential activation pathway 1-NP. Overall, our study identified contributor to trophoblastic functional impairment leading clarified specific mechanism via CYP1B1/ERK Our provided novel insights into new mechanisms reproductive toxicity pollutants.

Language: Английский

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Enhancing vulnerability of Afatinib using Erastin via xCT-mediated ROS/P38MAPK signaling feedback loop in gastric cancer cells

Gene, Journal Year: 2023, Volume and Issue: 873, P. 147468 - 147468

Published: May 10, 2023

Ferroptosis, being classified as a form of regulated cell death, was driven by the oxidative injury induced lipid peroxidation (LPO). Recently, ferroptosis has been confirmed to exert critical effect in pathogenesis and treatment various tumors, including gastric cancer (GC). Erastin, frequently used inducer, caused downregulating xCT expression resulting increasing reactive oxygen species (ROS) aggravating LPO. However, mechanisms Erastin regulation, especially GC, remain largely elusive. This work firstly demonstrated that inhibited growth promoted apoptosis AGS BGC823 cells. Then, based on Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analysis Erastin-related targets screened using PharmMapper Web, P38MAPK signaling explored validated BGC-823 Besides, Fer-1 P38 inhibitor were performed investigate depth. revealed feedback mode among xCT, ROS pathway, which affected each other. It meant through xCT-mediated ROS/P38MAPK loop. In addition, it noticed co-operation with cytotoxic effects Afatinib cells aggravated further strengthening activation pathway. summary, those works provided evidence plays an important role GC treated Afitinib. Furthermore, Erastin-induced via pathway loop provides new strategies for comprehensive treatment.

Language: Английский

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Anisomycin inhibits the activity of human ovarian cancer stem cells via regulating antisense RNA NCBP2‐AS2/MEK/ERK/STAT3 signaling

The Journal of Gene Medicine, Journal Year: 2023, Volume and Issue: 26(1)

Published: July 22, 2023

Abstract Background Ovarian cancer stem cells (OCSCs) are the main cause of relapse and drug resistance in patients with ovarian cancer. Anisomycin has been shown to be an effective antitumor agent, but its mechanism action remains elusive. Methods CD44+/CD133+ human OCSCs were isolated from tissues. interfered using anisomycin specific small‐interfering RNA (siRNA). Microarray assay, MTT, vivo tumorigenic experiments, transwell cell cycle colony formation angiogenesis hematoxylin eosin staining used detect respect inhibiting activity OCSCs. Expression NCBP2‐AS2/mitogen‐activated protein kinase (MEK)/extracellular signal‐regulated (ERK)/signal transducer activator transcription 3 (STAT3) pathway was examined western blotting, a quantitative real‐time PCR (RT‐qPCR) immunofluorescence staining. Bioinformatics analysis for predictive NCBP2‐AS2 expression urogenital tumors. Results showed that treatment significantly decreased antisense In vitro cellular experiments interfering endogenous siRNA distinctly inhibited proliferation, migration OCSCs, whereas animal revealed tumorigenesis nude mice. Moreover, results RT‐qPCR blotting demonstrated both silencing led significant reductions mRNA levels NCBP2‐AS2, MEK, ERK STAT3. From bioinformatic point view, exhibited differential between tumors normal controls, similar pattern found genes NCBP2, RPL35A, DNAJC19 ECE2, which have similarity NCBP2‐AS2. Conclusions suppresses by downregulating NCBP2‐AS2/MEK/ERK/STAT3 signaling pathway, potential serve as markers clinical diagnosis prognosis

Language: Английский

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miR-134-3p driven by anisomycin impairs ovarian cancer stem cell activity through inhibiting GPR137 expression

Journal of Cancer, Journal Year: 2023, Volume and Issue: 14(18), P. 3404 - 3415

Published: Jan. 1, 2023

Background: Ovarian cancer recurrence and metastasis are predominantly attributed to ovarian stem cells; however, the mechanism by which anisomycin regulates human cells (HuOCSCs) remains unclear. Methods: cDNA microArray was used screen microRNAs (miRNAs) targeted anisomycin, RT-qPCR validated miRNA targets. TargetScan database, GO enrichment analysis, RT-qPCR, accompanied a fluorescent reporter system, were employed verify target genes. In vitro experimental cell proliferation inhibition assay, flow cytometry, Transwell, angiogenesis in vivo transplantation tumor assay implemented assess ability of overexpressed miRNAs hinder HuOCSC activity. Western blot, immunofluorescence applied measure transcriptional protein-level expression genes their related Bioinformatic analysis predicted deciphered role development prognosis cancer. Results: The levels multiple DLK1-DIO3 imprinted microRNA cluster members altered among miR-134-3p most significantly elevated. overexpression suppressed screening validation uncovered that able markedly suppress GPR137 expression. Additionally, regulated cytoskeleton, migration-related protein NDEL1/DYNEIN/TUBA1A axis through targeting GPR137. Bioinformatics prediction unveiled close association GPR137, NDEL1, DYNC1H1, TUBA1A with prognosis. Conclusions: activity HuOCSCs may be compromised regulation miR-134-3p, inhibits GPR137/NDEL1/DYNEIN/TUBA1A axis.

Language: Английский

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Biosynthesis of the benzylpyrrolidine precursor in anisomycin by a unique ThDP-dependent enzyme

Synthetic and Systems Biotechnology, Journal Year: 2024, Volume and Issue: 10(1), P. 76 - 85

Published: Aug. 23, 2024

Language: Английский

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New Synthetic Analogs of Natural 5Z,9Z-Dienoic Acids—Hybrid Molecules Based on Oleanolic Acid: Synthesis and Study of Antitumor Activity

Cancers, Journal Year: 2024, Volume and Issue: 16(23), P. 3893 - 3893

Published: Nov. 21, 2024

: A series of synthetic analogs natural (5Z,9Z)-diene acids were synthesized for the first time in form hybrid molecules containing an oleanolic acid fragment. This fragment was simultaneously linked by amide bond to various hetero- and carbocyclic amines a complex ester (5Z,9Z)-tetradeca-5,9-dienecarboxylic acid, which new reaction Ti-catalyzed homocyclomagnification 1,2-dienes.

Language: Английский

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Curcumin analogue C66 ameliorates mouse cardiac dysfunction and structural disorders after acute myocardial infarction via suppressing JNK activation

European Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 946, P. 175629 - 175629

Published: March 1, 2023

Language: Английский

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