Total flavonoids of litchi seed inhibit breast cancer metastasis by regulating the PI3K/AKT/mTOR and MAPKs signaling pathways

Pharmaceutical Biology, Год журнала: 2025, Номер 63(1), С. 229 - 249

Опубликована: Апрель 15, 2025

Total flavonoids from Litchi chinensis Sonn. (Sapindaceae) seeds (TFLS) effectively attenuate stem cell-like properties in breast cancer cells. However, their pharmacological effects and mechanisms suppressing metastasis remain unclear. This study aimed to elucidate the inhibitory underlying of TFLS on metastasis. The antiproliferative, migratory, invasive activities cells following treatment were evaluated using CCK-8, wound-healing, transwell assays. epithelial-mesenchymal transition (EMT) biomarkers via Western blot analysis. anti-metastatic further validated vivo zebrafish mouse models. Network pharmacology methodology was utilized predict potential targets signaling pathways, which subsequently corroborated by blot. Potential active compounds identified through molecular docking, chemical constituents analyzed characterized UPLC-QTOF/MS. suppressed proliferation MDA-MB-231 MDA-MB-468 cells, with IC50 values 44.47 μg/mL 37.35 at 72 h, respectively. It vitro, demonstrated a marked reduction cellular motility invasiveness, alongside reversal EMT. Consistent pathway enrichment analysis, network revealed that reduced phosphorylation levels PI3K, AKT, mTOR, JNK, ERK, p38 Molecular docking seven ingredients, UPLC-MS/MS confirmed presence key compounds, including procyanidin A2. inhibits cell proliferation, migration, invasion vitro reversing EMT phenotype, while vivo. These are likely mediated attenuation PI3K/AKT/mTOR MAPK pathways.

Язык: Английский

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Anticancer Potential of Prebiotics: Targeting Estrogen Receptors and PI3K/AKT/mTOR in Breast Cancer

Biomedicines, Год журнала: 2025, Номер 13(4), С. 990 - 990

Опубликована: Апрель 18, 2025

Estrogen receptors (ERs) play a critical role in breast cancer (BC) development and progression, with ERα being oncogenic ERβ exhibiting tumor-suppressive properties. The interaction between ER signaling other molecular pathways, such as PI3K/AKT/mTOR, influences tumor growth endocrine resistance. Emerging research highlights the of prebiotics modulating gut microbiota, which may influence estrogen metabolism, immune function, therapeutic responses BC. This review explores impact on receptor modulation, microbiota composition, regulation, metabolic pathways cancer. potential adjunctive therapies to enhance treatment efficacy mitigate chemotherapy-related side effects is discussed. A comprehensive analysis recent preclinical clinical studies was conducted, examining reprogramming short-chain fatty acids (SCFAs) derived from prebiotic fermentation epigenetic regulation resistance also evaluated. Prebiotics were found modulate microbiota-estrogen axis, reduce inflammation, responses. SCFAs demonstrated selective downregulation reprogramming, suppressing growth. Synbiotic interventions effects, improving quality life patients. offer promising avenue for prevention therapy by pathways. Future trials are needed validate their treatments management.

Язык: Английский

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The Combined Effect of High-Intensity Interval Training and Time-Restricted Feeding on the AKT-IGF-1-mTOR Signaling Pathway in the Muscle Tissue of Type 2 Diabetic Rats

Nutrients, Год журнала: 2025, Номер 17(9), С. 1404 - 1404

Опубликована: Апрель 22, 2025

Background/Objectives: High-intensity interval training (HIIT) and time-restricted feeding (TRF) have shown potential in enhancing glucose metabolism, increasing insulin sensitivity, promoting muscle health. This study investigates the combined effects of HIIT TRF on AKT-IGF-1-mTOR signaling pathway tissue type 2 diabetic (T2D) rats. Methods: 42 male Wistar rats (4–5 weeks age) were included study. The animals randomly divided into two groups: 1. Standard diet (SD) non-diabetic (n = 7) 2. High-fat (HFD n 35) for 4 weeks. T2D was induced by intraperitoneal injection (IP) streptozotocin (STZ) at 35 mg/kg. Animals with blood levels ≥ 250 mg/dL considered diabetic. Diabetic five groups 7): Diabetes-HIIT (D-HIIT), Diabetes-TRF (D-T), 3. Diabetes-combined (D-T+HIIT), 4. Diabetes-Untreated Control (D), 5. Diabetes metformin (D-MET). protocol regimen followed 10 Muscle collected histological analysis, expression proteins related to measured. Results: Blood levels, resistance (IR), markers degradation significantly improved D-T+HIIT D-MET compared non-diabetes group. Furthermore, activation AKT mTOR proteins, as well increased IGF-1 expression, elevated group control other treatment groups, approached observed Additionally, fiber size overall structure particularly Conclusions: combination appears offer superior benefits improving protein synthesis, regulation rats, either or alone. These findings highlight this approach addressing muscle-related complications T2D.

Язык: Английский

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Exploring the therapeutic potential and in vitro validation of baicalin for the treatment of triple-negative breast cancer

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 28, 2025

To explore the mechanism of action baicalin (BA) in treatment triple-negative breast cancer (TNBC) based on network pharmacology, molecular docking and dynamics simulations vitro validation. The inhibitory effects different concentrations proliferation MDA-MB-231, 4T1, MCF-7, MCF-10A cell lines were evaluated by CCK8 assay with clone formation assay. Three compound target prediction platforms, Swiss Target Prediction, SEA Pharmmapper, used to predict baicalin-related targets, mapped cancer-related targets retrieved from GeneCards OMMI databases obtain potential for cancer; STRING database Cytoscape software construct protein interaction screen core targets; GO KEGG enrichment analyses performed binding key was verified simulation; expression relevant proteins verified. Baicalin showed more obvious antiproliferative at certain concentrations, had less effect normal cells. A total nine cancer, including AKT1, ESR1, TNF-α, SRC, EGFR, MMP9, JAK2, PPARG, GSK3B, identified through construction PPI interactions 'Traditional Chinese Medicine-Component-Target-Disease' network, a 252 related intersected analysis. analysis enriched 2,526 Biological process, 105 Cellular component 250 Molecular function intersecting 128 signaling pathways results studies found that able interact other breast, JAK2 proteins, significant changes levels proteins. inhibits TNF-α their cancer.

Язык: Английский

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Cannabidiol potentiates p53-driven autophagic cell death in non-small cell lung cancer following DNA damage: a novel synergistic approach beyond canonical pathways

Experimental & Molecular Medicine, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

The search for more effective and safer cancer therapies has led to an increasing interest in combination treatments that use well-established agents. Here we explore the potential of cannabidiol (CBD), a compound derived from cannabis, enhance anticancer effects etoposide non-small cell lung (NSCLC). Although CBD is primarily used manage childhood epilepsy, its broader therapeutic applications are being actively investigated, particularly oncology. Our results revealed that, among various tested chemotherapeutic drugs, showed most significant reduction NSCLC viability when combined with CBD. To understand this synergistic effect, conducted extensive transcriptomic proteomic profiling, which upregulated genes associated autophagic death while downregulating key oncogenes known drive tumor progression. This dual effect on oncogene suppression was mediated by inactivation PI3K-AKT-mTOR signaling pathway, crucial regulator growth survival, found be dependent p53 status. Interestingly, our analysis therapy did not rely traditional cannabinoid receptors or transient receptor cation channels, indicating exerts through novel, noncanonical mechanisms. findings suggest could represent groundbreaking approach treatment, cases where conventional fail. By inducing inhibiting oncogenic pathways, strategy offers promising new avenue enhancing treatment efficacy NSCLC, especially tumors function.

Язык: Английский

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