RESUMEN
Two new ent-clerodane diterpenoids, named isoscoparins R and S (1 and 2), were isolated from the aerial parts of Isodon scoparius. Their structures were characterized mainly by analyzing the NMR and HRESIMS data, and the relative configuration of compound 1 was determined by single-crystal X-ray diffraction. Compound 2 showed weak activity as an autophagic inhibitor.
Asunto(s)
Diterpenos de Tipo Clerodano/química , Diterpenos de Tipo Clerodano/farmacología , Isodon/química , Antineoplásicos Fitogénicos/química , Autofagia/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Células HEK293 , Células HeLa , Humanos , Inmunosupresores/farmacología , Espectroscopía de Resonancia Magnética , Estructura Molecular , Componentes Aéreos de las Plantas/química , Espectrometría de Masa por Ionización de Electrospray , Difracción de Rayos XRESUMEN
BACKGROUND: Lung cancer is a common kind of human malignancies. Lung squamous cell carcinoma (LUSC) is a key subtype of lung cancer. Cell cycle plays an important role in the development and occurrence of LUSC, however, there is still a lack of cell cycle-related genes in LUSC diagnosis and prediction of prognosis. METHODS: We identified differentially expressed genes (DEGs) with "limma" package in R software, and determined the biomarkers of LUSC in diagnosing by performing receiver operating characteristic (ROC) curve analysis, the biomarker effectiveness in diagnosing LUSC was assessed by performing five-fold cross-validation with logistic regression. Kaplan-Meier plot and the nomogram assessed the relationship between the biomarker and patient survival, and WB and qRT-PCR detected the biomarker expression in cells and tissues. Flow cytometry detects the role of the biomarker in the cell cycle. RESULTS: Integration analysis with The Cancer Genome Atlas (TCGA) database obtained a unique gene related to cell cycle in LUSC (Charged multivesicular body protein 4C, CHMP4C), and the protein of CHMP4C was highly expressed in LUSC tissues. ROC analysis indicated that CHMP4C was a biomarker for the diagnosis of LUSC. Bioinformatic analysis indicated that CHMP4C might be associated with cell cycle in LUSC. CHMP4C knockdown resulted in S-phase arrest of cells with LUSC. According to the survival rate analysis, CHMP4C overexpression indicated poor prognosis in patients with LUSC. CONCLUSIONS: CHMP4C regulates the proliferation process of tumor cells through the cell cycle. It can be used as a potential diagnostic and prognostic biomarker for LUSC.