Targeting Metabolic–Redox Nexus to Regulate Drug Resistance: From Mechanism to Tumor Therapy

Antioxidants, Год журнала: 2024, Номер 13(7), С. 828 - 828

Опубликована: Июль 10, 2024

Drug resistance is currently one of the biggest challenges in cancer treatment. With deepening understanding drug resistance, various mechanisms have been revealed, including metabolic reprogramming and alterations redox balance. Notably, mediates survival tumor cells harsh environments, thereby promoting development resistance. In addition, changes during pattern shift trigger reactive oxygen species (ROS) production, which turn regulates cellular metabolism, DNA repair, cell death, metabolism direct or indirect ways to influence sensitivity tumors therapies. Therefore, intersection ROS profoundly affects clarifying entangled may be beneficial for developing drugs treatment methods thwart this review, we will summarize regulatory mechanism on highlight recent therapeutic strategies targeting metabolic-redox circuits, dietary interventions, novel chemosynthetic drugs, combination regimens, delivery systems.

Язык: Английский

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Resveratrol and pancreatic cancers: Questions and future perspectives

World Journal of Gastrointestinal Oncology, Год журнала: 2025, Номер 17(3)

Опубликована: Фев. 13, 2025

There is still no effective treatment for pancreatic cancer, one of the deadliest malignancies among gastrointestinal diseases. Jiang et al demonstrated presence senescent cancer-associated fibroblasts (CAFs) in cancer tissues, supporting use CAFs as potential anti-cancer targets. The study indicated that a natural plant-derived compound resveratrol can reverse CAF phenotype and decrease growth, migration, invasiveness cells. Notably, might be involved regulating epithelial-to-mesenchymal transition tumor microenvironment. This editorial shares insights on future investigation signaling cells microenvironment, discusses resveratrol-based perspectives.

Язык: Английский

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Edgeworthia gardneri (Wall.) Meisn Mitigates CCL4-induced liver injury in mice by modulating gut microbiota, boosting antioxidant defense, and reducing inflammation

Ecotoxicology and Environmental Safety, Год журнала: 2025, Номер 293, С. 118042 - 118042

Опубликована: Март 1, 2025

Herbal medicine has become an area of growing global scientific interest. The prime objective this study was to investigate the protective role Edgeworthia gardneri (Wall.) Meisn (EGM polysaccharide) against carbon tetrachloride (CCl4)-induced liver injury in mice. Forty-five ICR mice were randomly divided into three groups (n = 15): IC, IM, and IT. IT group received EGM polysaccharide solution (50 mg/kg) daily, while IC IM administered equivalent volume normal saline. intraperitoneally injected with a mixture CCl4 olive oil at 1:1 (v/v) (2 mL/kg) every 3 days. Our results showed that significantly (p < 0.05) reduced pathological hepatic alterations increased index caused by CCl4. Moreover, therapy 0.001) levels antioxidant enzymes, such as glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), total capacity (T-AOC) malondialdehyde (MDA) content dose-dependent manner. Notably, alleviated inflammatory cascades evidenced decreased serum interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor- α (TNF-α) under administration. Furthermore, 16 s rRNA gene sequencing exhibited abundance probiotics bacteria, Unclassified_Lachnospiraceae, pathogenic bacterial texas like Brevundimonas Candidatus_Nitrocosmicu. Conclusively, protects CCl4-induced oxidative stress inflammation alleviates through beneficial gut microbiota modulations. current suggests is effective agent counteracting damage.

Язык: Английский

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Berberine Protects against Hepatocellular Carcinoma Progression by Regulating Intrahepatic T Cell Heterogeneity

Advanced Science, Год журнала: 2024, Номер 11(39)

Опубликована: Авг. 13, 2024

Abstract Accumulating evidence suggests that berberine (BBR) exhibits anti‐cancer effects in hepatocellular carcinoma (HCC). However, the mechanisms by which BBR regulates immunological microenvironment HCC has not been fully elucidated. In this study, a mouse model of orthotopic is established and treated with varying doses BBR. showed effectiveness reducing tumor burden mice HCC. Cytometry time‐of‐flight depicted alterations immune landscape following treatment, revealing enhancement T lymphocytes effector function. particular, decreased proportion TCRb hi PD‐1 CD69 + CD27 CD8 increased Ly6C CD62L central memory lymphocytes. Single‐cell RNA sequencing further elucidates on transcriptional profiles liver cells confirms phenotypical heterogeneity microenvironment. Additionally, it found potentially regulated antitumor immunity modulating receptor‐ligand interaction among mediated cytokines. summary, findings improve understanding BBR's impact protecting against HCC, emphasizing role regulating intrahepatic cell heterogeneity. potential to be promising therapeutic strategy hinder advancement

Язык: Английский

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Luteolin as an adjuvant effectively enhanced the efficacy of adoptive tumor-specific CTLs therapy

BMC Cancer, Год журнала: 2025, Номер 25(1)

Опубликована: Март 6, 2025

Luteolin, a natural flavonoid compound, has demonstrated anti-inflammatory, antioxidant, and broad anti-tumor properties. Recent studies suggest that its effects are linked to enhanced CTL function-including proliferation, survival, cytotoxicity-via inhibition of the YAP/Wnt signaling pathway in tumor cells. Consequently, luteolin potential as an adjuvant combination therapies with adoptive immunotherapy. This study first assessed luteolin's tumor-inhibitory vitro vivo using cytotoxicity assays, Transwell invasion tests, wound healing analyses post-treatment growth survival time. Additionally, we explored whether combined DC/tumor fusion vaccine could synergistically enhance overall antitumor efficacy by boosting activation, cytokines secretion, effector T Our findings indicate luteolin, standalone agent, can inhibit proliferation colon lung cancer cells both certain extent. When activated CTLs, it upregulated expression CD25 CD69 resulted higher levels IL-2, TNF-α, IFN-γ secretion vitro. In vivo, this significantly curtailed subcutaneous extended mean time tumor-bearing mice (HCT116, A549), outperforming monotherapy. Furthermore, therapy may be attributable apoptosis cells, reduced decreased YAP expression. The vaccine-activated CTLs presents novel approach for treatment. As adjuvant, downregulates enhancing cytotoxicity, thus improving recognition selective targeting. strategy is promising safe effective

Язык: Английский

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Antitumor and immunomodulatory activities of diphyllin and its derivatives

Bioorganic & Medicinal Chemistry, Год журнала: 2025, Номер unknown, С. 118197 - 118197

Опубликована: Апрель 1, 2025

Язык: Английский

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Thymoquinone enhances efficacy of cervical Cancer therapeutic vaccines via modulating CD8+ T cells

International Immunopharmacology, Год журнала: 2025, Номер unknown, С. 114605 - 114605

Опубликована: Май 1, 2025

Язык: Английский

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Antiproliferative and pro-apoptotic effects of Pseudevernia furfuracea (L.) Zopf extract and its active component physodic acid via oxidative stress and DNA damage in breast cancer cells

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Май 21, 2025

Mammary gland malignancies are the most diagnosed oncological diseases in women. The currently available treatment faces several problems, including resistance to cytostatics and relatively high recurrence rates. These limitations have led an increasing interest natural substances as potential anticancer agents. Therapeutic approaches using a combination of agent conventional cytostatic drug could also be beneficial minimising risk chemotherapy. In present study, we evaluated effect Pseudevernia furfuracea (L.) Zopf extract (PSE) isolated secondary metabolite physodic acid (PHY) vitro models breast cancer subtypes (ER+, HER2+, triple negative). To investigate effects tested compounds, range assays were employed. BrdU clonogenic used evaluate antiproliferative activity. Flow cytometry Western blot demonstrate apoptotic cell death, oxidative stress, DNA damage, immune checkpoint modulation time-dependent manner (24, 48, 72 h). PSE PHY induced cycle arrest at G1 with cycle-related proteins. Furthermore, activation intrinsic pathway, involving changes Bcl-2 family proteins, caspase-3/-7 activity, caspase-9 cleavage, cytochrome c release, PARP was detected all BC cells. Moreover, determined PSE- PHY-mediated generation ROS RNS, which damage response. Treatment cells resulted mitochondrial apoptosis associated stress damage. PD-1/PD-L1 demonstrated. Based on results, assume use promising targeted agents for BC.

Язык: Английский

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In Situ Injectable Sequentially Responsive Hydrogel Based on Triblock Copolymers for Breast Cancer Theranostic Amplification

Biomacromolecules, Год журнала: 2025, Номер unknown

Опубликована: Май 24, 2025

Celastrol (Cel), a natural small molecule, effectively inhibits breast cancer but has poor solubility and systemic toxicity. Herein, an in situ injectable sequentially responsive celastrol hydrogel (FCPC) based on the temperature-sensitive poloxamer F127 tumor-acidity-cleavable maleic acid amide is rationally designed. Once injected into tumor tissue, FCPC forms stable gel state rapidly, followed by continuously releasing activity molecules for five days. This thermosensitive drug delivery system extends residence time targeted release. The platform greatly strengthens Cel's antitumor ability both vitro vivo meanwhile reduces metastasis toxic side effects. Studies suggest may act suppressing PI3K-Akt MAPK pathways. Such intelligently solves administration problem caused of molecule potential clinical applicability.

Язык: Английский

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Promises of natural products as clinical applications for cancer

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2024, Номер 1880(1), С. 189241 - 189241

Опубликована: Дек. 12, 2024

Язык: Английский

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