Feiyanning formula (FYN) is a traditional Chinese medicine (TCM) prescription used for more than 20 years in the treatment of lung cancer. FYN is composed of Astragalus membranaceus, Polygonatum sibiricum, Atractylodes macrocephala, Cornus officinalis, Paris polyphylla, and Polistes olivaceous, etc. All of them have been proved to have anti-tumor effect. In this study, we used the TCM network pharmacological analysis to perform the collection of compound and disease target, the prediction of compound target and biological signal and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. It was found that the activation of mitochondrial pathway might be the molecular mechanism of the anti-lung cancer effect of FYN. The experimental results showed that FYN had an inhibitory effect on the growth of lung cancer cells in a dose-dependent and time-dependent manner. Moreover, FYN induced G₂/M cell cycle arrest and apoptotic cell death as early as 6 h after treatment. In addition, FYN significantly induced mitochondrial membrane depolarization and increased calreticulin expression. Metabolomics analysis showed the increase of ATP utilization (assessed by a significant increase of the AMP/ATP and ADP/ATP ratio, necessary for apoptosis induction) and decrease of polyamines (that reflects growth potential). Taken together, our study suggested that FYN induced apoptosis of lung adenocarcinoma cells by promoting metabolism and changing the mitochondrial membrane potential, further supporting the validity of network pharmacological prediction.

Cellular senescence exerts dual roles in lung cancer pathogenesis: initially suppressing tumorigenesis via p53/p21/p16-mediated cell cycle arrest, but promoting malignancy through the senescence-associated secretory phenotype (SASP). SASP secretes cytokines, proteases, and growth factors, reshaping the tumor microenvironment (TME) to drive immune evasion, metastasis, and therapy resistance. NF-κB activation induces APOBEC3B mutagenesis and PD-L1 overexpression, while mTOR signaling enhances glycolysis and OXPHOS to fuel tumor growth. Clinically, telomere attrition, p16/p21 expression, and SASP components serve as prognostic biomarkers. Therapeutic strategies target senescent cells and SASP. Future directions focus on single-cell multi-omics to decode senescence heterogeneity, spatially controlled drug delivery, and therapies targeting senescence-immune-metabolic crosstalk. By unraveling senescence’s dual regulatory mechanisms, this review highlights precision approaches to overcome resistance and improve lung cancer outcomes.

Previous studies of the neuroprotective activity of polyphenols have used ununiform culture systems, making it difficult to compare their neuroprotective potency. We have established a new and simple method for preparing differentiated PC12 cells by removing the toxic coating step. Cells were induced to differentiate with the nerve growth factor (NGF) in a serum-free medium, without a medium change, but with a one-time overlay supplementation of NGF. The optimal inoculation density of the cells was 6–12 × 10³ cells/cm², and the presence of serum inhibited the differentiation. Neuroprotective activity could be quantified by the specific index (SI) value, that is, the ratio of the 50% cytotoxic concentration to the 50% effective concentration. Alkaline extract from the leaves of Sasa senanensis Rehder (SE), having had hormetic growth stimulation, showed the highest SI value, followed by epigallocatechin gallate. The SI value of curcumin and resveratrol was much lower. This simple overly method, that can prepare massive differentiated neuronal cells, may be applicable for the study of the differentiation-associated changes in intracellular metabolites, and the interaction between neuronal cells and physiological factors.

Background/Aim: 4H-1-Benzopyran-4-ones (chromones) provide a backbone structure for the chemical synthesis of potent anticancer drugs. In contrast to 2-(N-cyclicamino)chromones, the biological activity of 3-(N-cyclicamino)chromones has not been reported. In this study, cytotoxicity of 15 3-(N-cyclicamino)chromone derivatives was investigated and subjected to quantitative structure–activity relationship (QSAR) analysis. Materials and Methods: Cytotoxicity against four human oral squamous cell carcinoma cell lines and three oral normal mesenchymal cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor-specificity (TS) was evaluated as the ratio of mean 50% cytotoxic concentration (CC₅₀) against normal oral cells to that against human oral squamous cell carcinoma cell lines. Potency-selectivity expression (PSE) value was calculated by dividing the TS value by the CC₅₀ against tumor cells. Apoptosis induction was evaluated by morphological observation, western blot analysis and cell-cycle analysis. For QSAR analysis, a total of 3,096 physicochemical, structural and quantum chemical features were calculated from the most stabilized structure optimized using CORINA. Results: 3-(4-phenyl-1-piperazinyl)-4H-1-benzopyran-4-one (3a) had the highest tumor specificity, comparable with that of melphalan, without induction of apoptosis. Compound 3a caused cytostatic growth inhibition and had much lower cytotoxicity against human oral keratinocytes compared to doxorubicin. TS of the 15 3-(N-cyclicamino)chromones was correlated with 3D structure and lipophilicity. Conclusion: Chemical modification of 3a may be a potential choice for designing a new type of anticancer drug.

Background/Aim: 4H-1-Benzopyran-4-ones (chromones) have provided backbone structure for the chemical synthesis of potent anticancer drugs. In this study, the cytotoxicity of fifteen 2-(N-cyclicamino)chromone derivatives was investigated and subjected to quantitative structure–activity relationship (QSAR) analysis. Materials and Methods: Cytotoxicity against four human oral squamous cell carcinoma cell lines and three oral normal mesenchymal cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor specificity (TS) was evaluated by ratio of mean 50% cytotoxic concentration (CC₅₀) against normal oral cells to that against human oral squamous cell carcinoma cell lines. Potency-selectivity expression (PSE) value was calculated by dividing the TS value by CC₅₀ against tumor cells. Apoptosis induction was evaluated by morphological observation, western blot analysis and cell-cycle analysis. For QSAR analysis, a total of 3,089 physicochemicals, structural and quantum chemical features were calculated from the most stabilized structure optimized using Corina. Results: 7-Methoxy-2-(4-morpholinyl)-4H-1-benzopyran-4-one (5c) showed highest tumor-specificity, comparable with that of doxorubicin, without inducing apoptosis. Tumor-specificity of fifteen 2-(N-cyclicamino) chromones was correlated with molecular shape, especially 3D-structure. Conclusion: Chemical modification of 5c may be a potential choice for designing a new type of anticancer drugs.