Ferroptosis: Potential opportunities for natural products in cancer therapy DOI

Anzheng Nie,

Chaozan Shen,

Zheng Zhou

et al.

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

Notch signaling pathway in cancer: from mechanistic insights to targeted therapies DOI Creative Commons

Qingmiao Shi,

Chen Xue,

Yifan Zeng

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 27, 2024

Notch signaling, renowned for its role in regulating cell fate, organ development, and tissue homeostasis across metazoans, is highly conserved throughout evolution. The receptor ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences, typically necessitating receptor-ligand interaction to initiate classical signaling transduction. Accumulating evidence indicates that the pathway serves as both an oncogenic factor a tumor suppressor various cancer types. Dysregulation of this promotes epithelial-mesenchymal transition angiogenesis malignancies, closely linked proliferation, invasion, metastasis. Furthermore, contributes maintaining stem-like properties cells, thereby enhancing invasiveness. regulatory metabolic reprogramming microenvironment suggests pivotal involvement balancing suppressive effects. Moreover, implicated conferring chemoresistance cells. Therefore, comprehensive understanding these biological processes crucial developing innovative therapeutic strategies targeting signaling. This review focuses on research progress cancers, providing in-depth insights into potential mechanisms regulation occurrence progression cancer. Additionally, summarizes pharmaceutical clinical trials therapy, aiming offer new human malignancies.

Language: Английский

Citations

84
Lactylation‐Driven IGF2BP3‐Mediated Serine Metabolism Reprogramming and RNA m6A—Modification Promotes Lenvatinib Resistance in HCC DOI Creative Commons
Yuanxiang Lu, Jinghan Zhu, Yuxin Zhang

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

Abstract Acquired resistance remains a bottleneck for molecular‐targeted therapy in advanced hepatocellular carcinoma (HCC). Metabolic adaptation and epigenetic remodeling are recognized as hallmarks of cancer that may contribute to acquired resistance. In various lenvatinib‐resistant models, increased glycolysis leads lactate accumulation lysine lactylation IGF2BP3. This is crucial capturing PCK2 NRF2 mRNAs, thereby enhancing their expression. process reprograms serine metabolism strengthens the antioxidant defense system. Additionally, altered increases availability methylated substrates, such S‐adenosylmethionine (SAM), N6‐methyladenosine (m6A) methylation mRNAs. The lactylated IGF2BP3‐PCK2‐SAM‐m6A loop maintains elevated levels, system promoting lenvatinib HCC. Treatment with liposomes carrying siRNAs targeting IGF2BP3 or inhibitor 2‐DG restored sensitivity vivo. These findings highlight connection between metabolic reprogramming regulation suggest pathways offer new strategies overcome

Language: Английский

Citations

18
Histone lactylation promotes multidrug resistance in hepatocellular carcinoma by forming a positive feedback loop with PTEN DOI Creative Commons
Yuan Zeng, Haoran Jiang, Zhoufeng Chen

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 31, 2025

Language: Английский

Citations

3
Glycolysis in the tumor microenvironment: a driver of cancer progression and a promising therapeutic target DOI Creative Commons
Junpeng Zhao, Dan-Dan Jin,

Mengxiang Huang

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: June 12, 2024

Even with sufficient oxygen, tumor cells use glycolysis to obtain the energy and macromolecules they require multiply, once thought be a characteristic of known as "Warburg effect". In fact, throughout process carcinogenesis, immune stromal cells, two major cellular constituents microenvironment (TME), also undergo thorough metabolic reprogramming, which is typified by increased glycolysis. this review, we provide full-scale review glycolytic remodeling several types TME show how these behave in acidic milieu created glucose shortage lactate accumulation result Notably, an overview putative targets inhibitors along viability using combination immunotherapy chemotherapy. Understanding situations diverse within immunological will aid creation subsequent treatment plans.

Language: Английский

Citations

14
Polyphenol nanocomplex modulats lactate metabolic reprogramming and elicits immune responses to enhance cancer therapeutic effect DOI Creative Commons
Zhan Zhang, Xinnan Li, Weiqiang Liu

et al.

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: unknown, P. 101060 - 101060

Published: Jan. 1, 2024

Cancer lactate metabolic reprogramming induces an elevated level of extracellular and H+, leading to acidic immunosuppressive tumor microenvironment (TEM). High lactic acid may affect the programs various cells that comprise antitumor immune response, therefore, restricting immune-mediated destruction, therapeutic resistance unsatisfactory prognosis. Here, we report a metal-phenolic coordination-based nanocomplex loaded with natural polyphenol galloflavin, which inhibits function dehydrogenase, reducing production acid, alleviating TME. Besides, co-entrapped carnosic synthetic PEG-Ce6 derivative (serving as photosensitizer) could induce immunogenic cancer cell death upon laser irradiation, further activates system promotes recruitment infiltration in tissues. We demonstrated this nanocomplex-based combinational therapy reshape TME elicit responses murine breast model, provides promising strategy enhance efficiency drug-resistant cancer.

Language: Английский

Citations

11
New Opportunities in the Systemic Treatment of Hepatocellular Carcinoma—Today and Tomorrow DOI Open Access
Rafał Becht, Kajetan Kiełbowski, Michał Wasilewicz

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1456 - 1456

Published: Jan. 25, 2024

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Liver cirrhosis, hepatitis B, C, and non-alcoholic fatty disease represent major risk factors of HCC. Multiple different treatment options are available, depending on Barcelona Clinic Cancer (BCLC) algorithm. Systemic reserved for certain patients in stages B who will not benefit from regional methods. In last fifteen years, arsenal available therapeutics has largely expanded, which improved outcomes. Nevertheless, all respond to these agents novel combinations drugs needed. this review, we aim summarize pathway trials investigating safety efficacy targeted immunotherapies since introduction sorafenib. Furthermore, discuss current evidence regarding resistance mechanisms potential targets advanced

Language: Английский

Citations

10
LncRNA PWRN1 inhibits the progression of hepatocellular carcinoma by activating PKM2 activity DOI Creative Commons

Mingming Fei,

Xianying Li,

Shuhang Liang

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 584, P. 216620 - 216620

Published: Jan. 11, 2024

Hepatocellular carcinoma (HCC) is one of the most prevalent and leading causes cancer-related mortality worldwide. Long non-coding RNAs (lncRNAs) have been demonstrated to play vital roles in cancer development progression. The lncRNA PWRN1 (PWRN1), acts as a tumor suppressor factor, which low expressed some cancers. However, molecular mechanisms underlying effects PWRN1, especially regulatory relationship with RNA binding protein HCC remain largely unknown. In present study, we that was significantly down-regulated correlated better prognosis; furthermore, gain-of-function experiments showed inhibited proliferation cells. We further found up-regulated pyruvate kinase activity thus hinders vitro vivo. Mechanistically, M2 (PKM2) bound it maintained high state PKM2, thereby hindering PKM2 from entering nucleus form low-activity dimers, reducing expression c-Myc downstream gene LDHA, decrease lactate levels, inhibiting growth addition, inhibit aerobic glycolysis. Finally, TEPP-46, activator, appeared by maintaining tetramer stability increasing activity. Taken together, our results provide new insights into biology indicate combination activators might represent novel therapeutic target for HCC.

Language: Английский

Citations

9
Modulation of almonertinib resistance in non-small cell lung cancer by cancer-associated fibroblasts through HK2-mediated glycolysis and SKP2 signaling DOI Creative Commons

Guohao Wei,

Lingyao Fan,

Xiaoyan Song

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 15, 2025

Almonertinib is a third-generation EGFR-TKI, and studies on its resistance mechanisms are lacking. Cancer-associated fibroblasts (CAFs) can influence to targeted therapeutics, but their role mechanism of action in relation almonertinib unclear. The study explored relationships among glycolysis, cancer-associated (CAFs), resistance. A dose-escalation method was used develop the almonertinib-resistant cell line H1975AR. Hexokinase 2 (HK2) effects were evaluated using Cell Counting Kit-8 assays, transcriptome sequencing, western blotting, real-time PCR, siRNA glucose consumption, lactate production assays. Differential gene expression analysis assays H1975 cells cultured with CAF-conditioned medium (H1975/CAF-CM) revealed S-phase kinase-associated protein (SKP2) as target driving HK2. impact HK2 inhibitors H1975/CAF-CM assessed colony formation, wound healing, transwell, flow cytometry apoptosis H1975AR displayed elevated glycolysis Subsequently, we showed that knockdown reduced cells. induced upregulation HK2, which reversed by SKP2. CAFs regulate HK2-mediated through SKP2, promoting NSCLC. promotes

Language: Английский

Citations

1
Integrated analysis of histone lysine lactylation (Kla)-specific genes suggests that NR6A1, OSBP2 and UNC119B are novel therapeutic targets for hepatocellular carcinoma DOI Creative Commons

Qinjuan Wu,

Xin Li,

Menghong Long

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Oct. 30, 2023

Histone lysine lactylation (Kla) plays a vital role in the tumorigenesis of hepatocellular carcinoma (HCC). Hence, we focused on Kla-specific genes to select novel therapeutic targets. Differentially expressed (DEKlaGs) were identified from TCGA with cut-off criteria |log2(FlodChange (FC))| > 2, p-value < 0.05, following investigating prognostic value. The correlation between lactate accumulation and DEKlaGs expression was further investigated. On other hand, explored roles Kla activation immune microenvironment, immunotherapy, drug resistance. We conducted gene set enrichment analysis (GSEA) predict pathways influenced by Kla. predictive power Cox model ICGC GEO databases. A total 129 identified, 32 molecules might be potential biomarkers. including ARHGEF37, MTFR2, NR6A1, NT5DC2, OSBP2, RNASEH2A, SFN, UNC119B constructed, which suggested unfavorable overall survival high-risk score group, risk could serve as an indicator for large tumor size, poor pathological grade advanced stage. OSBP2 inhibit NK cell well TIL infiltration, impair Type-I II IFN responses HCC, thereby contributing unsatisfactory prognosis immunotherapy related chemotherapy GSEA showed that WNT, MTOR, MAPK NOTCH signaling activated, indicating these play crucial during process. NR6A1 overexpressed GEO. contributed stage ICGC. In summary, histone HCC independent biomarker. associated prognosis, resistance, suggesting candidate targets HCC.

Language: Английский

Citations

18
HDAC Inhibition Sensitize Hepatocellular Carcinoma to Lenvatinib via Suppressing AKT Activation DOI Creative Commons
Shuai Yan, Lu Chen, Hao Zhuang

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(8), P. 3046 - 3060

Published: Jan. 1, 2024

Hepatocellular carcinoma (HCC) is a deadly malignancy with limited treatment options.As first-line for advanced HCC, Lenvatinib has been applicated in clinic since 2018.Resistance to Lenvatinib, however, severely restricted the clinical benefits of this drug.Therefore, it urgent explore potential resistance mechanisms and identify appropriate methods reduce HCC.We identified SAHA, HDAC inhibitor, have effective anti-tumor activity against Lenvatinib-resistant HCC organoids by screening customized drug library.Mechanism analysis revealed that SAHA upregulates PTEN expression suppresses AKT signaling, which contributes reversing liver cancer cells.Furthermore, combinational application inhibitor or synergistically inhibits cell proliferation induces apoptosis.Finally, we confirmed synergistic effects AZD5363 primary patient derived organoids.Collectively, these findings may enable development combination therapies HCC.

Language: Английский

Citations

6