Role of natural products in tumor therapy from basic research and clinical perspectives

Acta Materia Medica, Journal Year: 2024, Volume and Issue: 3(2)

Published: Jan. 1, 2024

Cancer is the leading cause of morbidity and mortality worldwide an important barrier to lengthening life expectancy in every country. Natural products are receiving increased attention from researchers globally increasing numbers natural approved for clinical studies involving cancer recent years. To gain more insight into that have undergone trials treatment, a comprehensive search was conducted. The https://clinicaltrials.gov website searched relevant product information up December 2022. terms included different types cancers, such as colorectal, lung, breast, gynecologic, kidney, bladder, melanoma, pancreatic, hepatocellular, gastric haematologic. Then, PubMed Web Science were articles February 2024. Hence, we listed existing about used treatment cancers discussed preclinical some promising their targets, indications, underlying mechanisms action. Our intent provide basic readers who interested or majoring obtain deeper understanding progress actions

Language: Английский

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CSF1R inhibition reprograms tumor-associated macrophages to potentiate anti-PD-1 therapy efficacy against colorectal cancer

Pharmacological Research, Journal Year: 2024, Volume and Issue: 202, P. 107126 - 107126

Published: March 1, 2024

PD-1 blockade therapy has made great breakthroughs in treatment of multiple solid tumors. However, patients with microsatellite-stable (MSS) colorectal cancer (CRC) respond poorly to anti-PD-1 immunotherapy. Although CRC microstatellite instability (MSI) or microsatellite instability-high (MSI-H) can benefit from therapy, there are still some problems such as tumor recurrence. Tumor-associated macrophages (TAMs), most abundant immune components microenvironment (TME), largely limit the therapeutic efficacy against CRC. The CSF1/CSF1R pathway plays a key role regulating macrophage polarization, and blocking CSF1R signaling transduction may be potential strategy effectively reprogram remodel TME. Here, we found that increasing expression predicted poor prognosis cohort. Furthermore, discovered novel potent inhibitor, PXB17, which significantly reprogramed M2 M1 phenotype. Mechanically, PXB17 blocked activation PI3K/AKT/mTORC1 signaling, resulting inhibition cholesterol biosynthesis. Results 3D co-culture system suggested PXB17-repolarized could induce infiltration CD8+ T lymphocytes tumors improve immunosuppressive microenvironment. In vivo, halted growth, stronger effect than PLX3397. particular, potently enhanced activity mAb CT-26 model prevented recurrence MC-38 by promoting formation long-term memory immunity. Our study opens new avenue for innate adaptive anti-tumor immunomodulatory suggests is promising immunotherapy molecule enhancing reducing

Language: Английский

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Single-cell transcriptomics reveals the ameliorative effect of rosmarinic acid on diabetic nephropathy-induced kidney injury by modulating oxidative stress and inflammation

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(4), P. 1661 - 1676

Published: Jan. 11, 2024

Diabetic nephropathy (DN) is a severe complication of diabetes, characterized by changes in kidney structure and function. The natural product rosmarinic acid (RA) has demonstrated therapeutic effects, including anti-inflammation anti-oxidative-stress, renal damage or dysfunction. In this study, we the heterogeneity cellular response kidneys to DN-induced injury RA treatment at single cell levels. Our results that significantly alleviated tubular epithelial injury, particularly proximal S1 segment on glomerular cells known as podocytes, while attenuating inflammatory macrophages, oxidative stress, cytotoxicity killer cells. These findings provide comprehensive understanding mechanisms which alleviates damage, inflammation, offering valuable guidance for clinical application DN.

Language: Английский

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Epigenomic heterogeneity as a source of tumour evolution

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 16, 2024

Language: Английский

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Targeting MAPK14 by Lobeline Upregulates Slurp1‐Mediated Inhibition of Alternative Activation of TAM and Retards Colorectal Cancer Growth

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

Published: Jan. 22, 2025

Abstract Colorectal cancer (CRC) usually creates an immunosuppressive microenvironment, thereby hindering immunotherapy response. Effective treatment options remain elusive. Using scRNA‐seq analysis in a tumor‐bearing murine model, it is found that lobeline, alkaloid from the herbal medicine lobelia, promotes polarization of tumor‐associated macrophages (TAMs) toward M1‐like TAMs while inhibiting their M2‐like TAMs. Additionally, lobeline upregulates mRNA expression secreted Ly‐6/UPAR‐related protein 1 ( Slurp1 ) cells. The inhibitory effects on tumor load and TAM are almost completely eliminated when Slurp1‐deficient MC38 cells subcutaneously injected into mice, suggesting exerts antitumor effect Slurp1‐dependent manner. Furthermore, using target‐responsive accessibility profiling, MAPK14 identified as direct target lobeline. Mechanistically, upon binding to colon cells, prevents nuclear translocation MAPK14, resulting decreased levels phosphorylated p53. Consequently, negative transcriptional regulation SLURP1 by p53 suppressed, leading enhanced transcription secretion SLURP1. Finally, combination therapy anti‐PD1 exhibits stronger effects. Taken together, these findings suggest remodeling microenvironment small‐molecule may represent promising therapeutic strategy for CRC.

Language: Английский

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Impact of cannabinoids on cancer outcomes in patients receiving immune checkpoint inhibitor immunotherapy

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 5, 2025

Cannabinoids relieve pain, nausea, anorexia and anxiety, improve quality of life in several cancer patients. The immunotherapy with checkpoint inhibitors (ICIs), although very successful a subset patients, is accompanied by moderate to severe immune-related adverse events (ir-AE) that often necessitate its discontinuation. Because their role symptomatic relief, cannabinoids have been used combination immune inhibitor (ICI) immunotherapy. A few studies strongly suggest the use medicinal cannabis patients attenuates many ir-AE associated ICI increase tolerability. However, no significant beneficial effects on overall survival, progression free survival or relapses were observed; rather, some noted concurrent administration clinical benefits latter. cannabinoids' well documented immunosuppressive mediated through cannabinoid recptor-2 (CB2), we propose considering this receptor as an inhibitory per se. simultaneous neutralization CB2, treatment, may lead better outcomes receiving In regard, such cannabidiol (CBD) cannabigerol (CBG), little agonism for be therapeutic choices. Additional strategies e.g., monoacylglycerol lipase (MAGL) degrade endocannabinoids lipogenesis formation lipid bilayers cells also explored. Future should take into consideration gut microbiota, CYP450 polymorphism haplotypes, cannabinoid-drug interactions genetic somatic variations occurring receptors signaling pathways personalized cannabis-based therapies ICIs. This rational knowledge-based regimens tailored individual

Language: Английский

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Hi-C, a chromatin 3D structure technique advancing the functional genomics of immune cells

Frontiers in Genetics, Journal Year: 2024, Volume and Issue: 15

Published: March 22, 2024

The functional performance of immune cells relies on a complex transcriptional regulatory network. three-dimensional structure chromatin can affect status and gene expression patterns, plays an important role in transcription. Currently available techniques for studying spatial include conformation capture their derivatives, accessibility sequencing techniques, others. Additionally, the recently emerged deep learning technology be utilized as tool to enhance analysis data. In this review, we elucidate definition significance structure, summarize technologies it, describe research progress dendritic cells, macrophages, T B neutrophils.

Language: Английский

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Monotropein represses the proliferation and angiogenesis via the AKT/NF-κB pathway in lung cancer

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Language: Английский

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Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 3, 2025

Abstract Transcriptional dysregulation is a hallmark of cancer initiation and progression, driven by genetic epigenetic alterations. Enhancer reprogramming has emerged as pivotal driver carcinogenesis, with cells often relying on aberrant transcriptional programs. The advent high-throughput sequencing technologies provided critical insights into enhancer events their role in malignancy. While targeting enhancers presents promising therapeutic strategy, significant challenges remain. These include the off-target effects enhancer-targeting technologies, complexity redundancy networks, dynamic nature reprogramming, which may contribute to resistance. This review comprehensively encapsulates structural attributes enhancers, delineates mechanisms underlying malignant transformation, evaluates opportunities limitations associated cancer.

Language: Английский

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Gallic Acid Inhibits the Proliferation and Migration of Ovarian Cancer Cells via Inhibition of the PI3K‐AKT Pathway and Promoting M1‐Like Macrophage Polarization

Analytical Cellular Pathology, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Language: Английский

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