Traditional Chinese medicine for colorectal cancer treatment: potential targets and mechanisms of action

Chinese Medicine, Journal Year: 2023, Volume and Issue: 18(1)

Published: Feb. 13, 2023

Colorectal cancer (CRC) is a disease with complex pathogenesis, it prone to metastasis, and its development involves abnormalities in multiple signaling pathways. Surgery, chemotherapy, radiotherapy, target therapy, immunotherapy remain the main treatments for CRC, but improvement overall survival rate quality of life urgently needed. Traditional Chinese medicine (TCM) has long history preventing treating CRC. It could affect CRC cell proliferation, apoptosis, cycle, migration, invasion, autophagy, epithelial-mesenchymal transition, angiogenesis, chemoresistance by regulating pathways, such as PI3K/Akt, NF-κB, MAPK, Wnt/β-catenin, epidermal growth factor receptors, p53, TGF-β, mTOR, Hedgehog, immunomodulatory In this paper, pathways potential targets TCM active ingredients treatment were systematically summarized, providing theoretical basis new ideas further exploring pathogenesis developing anti-CRC drugs.

Language: Английский

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PIWI-interacting RNA-YBX1 inhibits proliferation and metastasis by the MAPK signaling pathway via YBX1 in triple-negative breast cancer

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Jan. 5, 2024

Abstract Breast cancer is the second leading cause of death in women worldwide, with triple-negative breast (TNBC) having worst prognosis. Although there are numerous studies on TNBC, no effective treatment for it, and it still a major problem today. Studies PIWI-interacting RNAs (piRNAs) increasing investigating mechanism piRNAs proliferation metastasis TNBC may lead to new potential targets. Here, we identified novel piRNA, piR-YBX1, which was downregulated compared matched normal tissue. Overexpression piR-YBX1 significantly inhibited proliferation, migration, invasion ability cells both vivo vitro. Mechanistically, could bind directly mRNA Y-box binding protein 1 ( YBX1 ) overexpression levels, while function be partly rescued by YBX1. In addition, RAF1 key molecule MAPK signaling pathway, p-MEK p-ERK1/2, can reverted conclusion, our findings discovered that piR-YBX1/YBX1/MAPK axis suppresses therefore has an therapeutic agent cancer.

Language: Английский

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PD-1/PD-L1 and DNA Damage Response in Cancer

Cells, Journal Year: 2023, Volume and Issue: 12(4), P. 530 - 530

Published: Feb. 7, 2023

The application of immunotherapy for cancer treatment is rapidly becoming more widespread. Immunotherapeutic agents are frequently combined with various types treatments to obtain a durable antitumor clinical response in patients who have developed resistance monotherapy. Chemotherapeutic drugs that induce DNA damage and trigger (DDR) an increase the expression programmed death ligand-1 (PD-L1) can be employed by cells avoid immune surveillance. PD-L1 exposed on turn targeted re-establish immune-reactive tumor microenvironment, which ultimately increases tumor’s susceptibility therapies. Here we review recent advances how DDR regulates point out effect etoposide, irinotecan, platinum compounds anti-tumor response.

Language: Английский

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Strategy of targeting the tumor microenvironment via inhibition of fibroblast/fibrosis remodeling new era to cancer chemo-immunotherapy resistance

European Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 957, P. 175991 - 175991

Published: Aug. 23, 2023

Language: Английский

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The ERK-cPLA2-ACSL4 axis mediating M2 macrophages ferroptosis impedes mucosal healing in ulcerative colitis

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 214, P. 219 - 235

Published: Feb. 15, 2024

Language: Английский

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Exploring the Key Signaling Pathways and ncRNAs in Colorectal Cancer

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4548 - 4548

Published: April 21, 2024

Colorectal cancer (CRC) is the third most prevalent to be diagnosed, and it has a substantial mortality rate. Despite numerous studies being conducted on CRC, remains significant health concern. The disease-free survival rates notably decrease as CRC progresses, emphasizing urgency for effective diagnostic therapeutic approaches. development caused by environmental factors, which mostly lead disruption of signaling pathways. Among these pathways, Wingless/Integrated (Wnt) pathway, Phosphatidylinositol 3-kinase/protein kinase B/mammalian target rapamycin (PI3K/AKT/mTOR) Mitogen-Activated Protein Kinase (MAPK) Transforming Growth Factor-β (TGF-β) p53 pathway are considered important. These pathways also regulated non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long (lncRNAs), circular (circRNAs). They have emerged crucial regulators gene expression in changing their levels. altered patterns ncRNAs been implicated progression development, suggesting potential targets. This review provides an overview five key regulation involved pathogenesis that studied identify promising avenues diagnosis treatment strategies.

Language: Английский

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Dual Targeting of MEK1 and Akt Kinase Identified SBL‐027 as a Promising Lead Candidate to Control Cell Proliferations in Gastric Cancer

Biotechnology and Applied Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

ABSTRACT Dual inhibition of Akt and MEK1 pathways offers a promising strategy to enhance treatment efficacy in gastric cancer. In this study, we employed computational approaches followed by vitro validations. Our results demonstrate that SBL‐027 exhibits robust enduring interactions with kinases, as evidenced atomistic molecular dynamics simulations mechanics Poisson–Boltzmann surface area (MM‐PBSA) based binding free energy estimates. The predicted Gibbs energies indicate highly favorable between both kinases. vitro, displayed an IC 50 value 195.20 nM against 239.10 enzymes. compound exhibited potent cell proliferation KATOIII SNU‐5 cells, GI values 490.70 615.14 nM, respectively. Moreover, induced increase the sub G 0 /G 1 population during cycle while facilitating early late‐phase apoptosis these lines. Notably, significantly reduced percentage dual‐positive cells expressing cancer cells. strong affinity, stability, thermodynamics along established highlight its potential lead for further preclinical clinical development.

Language: Английский

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Anti-Inflammatory and Anti-Migratory Effects of Morin on Non-Small-Cell Lung Cancer Metastasis via Inhibition of NLRP3/MAPK Signaling Pathway

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 103 - 103

Published: Jan. 10, 2025

Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths globally, with a persistently low five-year survival rate only 14–17%. High rates metastasis contribute significantly to poor prognosis NSCLC, in which inflammation plays an important role by enhancing tumor growth, angiogenesis, and metastasis. Targeting inflammatory pathways within cells may thus represent promising strategy for inhibiting NSCLC This study evaluated anti-inflammatory anti-metastatic properties morin, bioactive compound derived from Thai medicinal herb, focusing on its effects NLRP3 inflammasome-mediated vitro model. The A549 H1299 cell lines were stimulated lipopolysaccharide (LPS) adenosine triphosphate (ATP) activate pathway. inhibition exhibited morin reducing pro-inflammatory secretion LPS- ATP-stimulated assessed ELISA, while wound healing trans-well invasion assays impact migration invasion. RT-qPCR measurement quantified expression genes, zymography Western blotting used examine changes invasive protein levels, epithelial-to-mesenchymal transition (EMT) markers, underlying molecular mechanisms. Our findings demonstrated significant ability decrease production IL-1β, IL-18, IL-6 dose-dependent manner (p < 0.05), as well suppress Morin downregulated proteins (MMP-2, MMP-9, u-PAR, u-PA, MT1-MMP) EMT markers (fibronectin, N-cadherin, vimentin) 0.01) also mRNA levels NLRP3, IL-6. Mechanistic investigations revealed that suppressed inflammasome activity inactivated MAPK pathways. Specifically, it decreased ASC reduced caspase-1 activity, phosphorylation ERK, JNK, p38 proteins. Collectively, these suggest morin’s inactivation pathway could offer novel therapeutic counteracting pro-tumorigenic metastatic progression NSCLC.

Language: Английский

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Pyrimidine scaffold dual‐target kinase inhibitors for cancer diseases: A review on design strategies, synthetic approaches, and structure–activity relationship (2018‒2023)

Archiv der Pharmazie, Journal Year: 2025, Volume and Issue: 358(1)

Published: Jan. 1, 2025

Abstract Cancer, the second leading cause of death globally, causes a significant threat to life. Despite advancements in treatment cancer, persistent challenges include severe side effects and emergence acquired drug resistance. Additionally, many traditional chemotherapy drugs show restricted efficacy high toxicity, primarily attributed their lack selectivity. Thus, development targeting protein kinases has emerged as noteworthy priority for addressing human cancers. Medicinal chemists have shown considerable interest dual candidates strategy create medicines that are safer, more efficient, cost‐effective. Furthermore, Food Drug Administration (FDA) approved several dual‐target anticancer treatment, emphasizing lower risks interactions improved pharmacokinetics safety profiles. This review focuses on synthetic efforts, design strategies, structure–activity relationship pyrimidine scaffold‐based kinase inhibitors developed with potential within recent 6 years (2018‒2023). Collectively, these strategies expected offer fresh perspectives future directions pyrimidine‐based design, potentially advancing cancer therapeutics.

Language: Английский

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Tumor dormancy and relapse: understanding the molecular mechanisms of cancer recurrence

Military Medical Research, Journal Year: 2025, Volume and Issue: 12(1)

Published: Feb. 11, 2025

Abstract Cancer recurrence, driven by the phenomenon of tumor dormancy, presents a formidable challenge in oncology. Dormant cancer cells have ability to evade detection and treatment, leading relapse. This review emphasizes urgent need comprehend dormancy its implications for recurrence. Despite notable advancements, significant gaps remain our understanding mechanisms underlying lack reliable biomarkers predicting provides comprehensive analysis cellular, angiogenic, immunological aspects dormancy. It highlights current therapeutic strategies targeting dormant cells, particularly combination therapies immunotherapies, which hold promise preventing By elucidating these proposing innovative research methodologies, this aims deepen ultimately facilitating development more effective recurrence improving patient outcomes.

Language: Английский

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