RESUMO
1,3,4-Oxadiazole derivatives are among the most studied anticancer drugs. Previous studies have analyzed the action of different 1,3,4-oxadiazole derivatives and their effects on cancer cells. This study investigated the characterization of two new compounds named 6 and 14 on HeLa and PC-3 cancer cell lines. Based on the previously obtained IC50, cell cycle effects were monitored by flow cytometry. RNA sequencing (RNAseq) was performed to identify differentially expressed genes, followed by functional annotation using gene ontology (GO), KEGG signaling pathway enrichment, and protein-protein interaction (PPI) network analyses. The tubulin polymerization assay was used to analyze the interaction of both compounds with tubulin. The results showed that 6 and 14 strongly inhibited the proliferation of cancer cells by arresting them in the G2/M phase of the cell cycle. Transcriptome analysis showed that exposure of HeLa and PC-3 cells to the compounds caused a marked reprograming of gene expression. Functional enrichment analysis indicated that differentially expressed genes were significantly enriched throughout the cell cycle and cancer-related biological processes. Furthermore, PPI network, hub gene, and CMap analyses revealed that compounds 14 and 6 shared target genes with established microtubule inhibitors, indicating points of similarity between the two molecules and microtubule inhibitors in terms of the mechanism of action. They were also able to influence the polymerization process of tubulin, suggesting the potential of these new compounds to be used as efficient chemotherapeutic agents.
Assuntos
Antineoplásicos , Calcogênios , Neoplasias , Humanos , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Relação Estrutura-Atividade , Proliferação de Células , Antineoplásicos/farmacologia , Células HeLa , Moduladores de Tubulina/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
The fight against cancer is one of the main challenges for medical research. Recently, nanotechnology has made significant progress, providing possibilities for developing innovative nanomaterials to overcome the common limitations of current therapies. In this context, silver nanoparticles (AgNPs) represent a promising nano-tool able to offer interesting applications for cancer research. Following this path, we combined the silver proprieties with Artemisia arborescens characteristics, producing novel nanoparticles called Artemisia-AgNPs. A "green" synthesis method was performed to produce Artemisia-AgNPs, using Artemisia arborescens extracts. This kind of photosynthesis is an eco-friendly, inexpensive, and fast approach. Moreover, the bioorganic molecules of plant extracts improved the biocompatibility and efficacy of Artemisia-AgNPs. The Artemisia-AgNPs were fully characterized and tested to compare their effects on various cancer cell lines, in particular HeLa and MCF-7. Artemisia-AgNPs treatment showed dose-dependent growth inhibition of cancer cells. Moreover, we evaluated their impact on the cell cycle, observing a G1 arrest mediated by Artemisia-AgNPs treatment. Using a clonogenic assay after treatment, we observed a complete lack of cell colonies, which demonstrated cell reproducibility death. To have a broader overview on gene expression impact, we performed RNA-sequencing, which demonstrated the potential of Artemisia-AgNPs as a suitable candidate tool in cancer research.
Assuntos
Antineoplásicos , Apoptose/efeitos dos fármacos , Artemisia/química , Nanopartículas Metálicas , Prata , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Apoptose/genética , Artemisia/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Química Verde , Células HeLa , Humanos , Células MCF-7 , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Células PC-3 , Extratos Vegetais/química , Prata/química , Prata/uso terapêuticoRESUMO
We investigated the responses of community structure of soil arthropods to yak and Tibetan sheep grazing based on a manipulated grazing experiment at the alpine meadow livestock Adaptive Management Platform, which locates in Haiyan County, Qinghai Province. The results showed that the obtained soil arthropods belonged to 26 families, 8 orders, and 4 classes, with Acaroidae and Oribatida as the dominant groups. Yak and Tibetan sheep grazing decreased the abundance but increased Shannon index, Margalef index and Pielou index of soil arthropods. Yak grazing significantly increased the quantity of the predatory soil arthropod groups. Yak and Tibetan sheep gra-zing significantly increased the quantity of the detritivore soil arthropod groups, but did not affect the quantity of the omnivorous and phytophagous soil arthropod groups. Yak and Tibetan sheep grazing significantly reduced the abundance of soil mites. Soil bulk density, available potassium, and available nitrogen were the main abiotic factors affecting soil arthropods community composition.
Assuntos
Artrópodes , Humanos , Animais , Bovinos , Ovinos , Tibet , Pradaria , Solo/química , ChinaRESUMO
Objective: This study was designed to analyze the expression of CSNK1D in hepatocellular carcinoma (HCC) and investigate the relationship between the expression of CSNK1D and the prognosis of HCC patients. Methods: The CSNK1D and alpha-fetoprotein (AFP) expression levels in patients with HCC and their corresponding clinical data were downloaded from The Cancer Genome Atlas (TCGA) and sorted with a Perl program. CSNK1D and AFP expression differences in liver tissue and liver cancer were compared and analyzed, based on the online database human cancer metastasis database, the relationships between the expression levels of CSNK1D and AFP and the proliferation and metastases of HCC were explored. The immunohistochemical data obtained from the Human Protein Atlas Database further verified the differences in the expression levels of CSNK1D and AFP in liver tissues and liver cancer tissues. Through Kaplan-Meier survival analysis, the effects of CSNK1D and AFP expression levels on the prognosis of patients with HCC were investigated, and the influences of and patients' gender, age and grades of cancer cells, tumor size, the status of lymph node metastasis, distant metastasis, and tumor stage on the expression of CSNK1D were analyzed with R language. The influence of differential expressions of CSNK1D on survival time was compared and the prognostic factors influencing the survival of HCC patients were statistically explored by univariate analysis and multivariate analysis. The potential influencing mechanism of CSNK1D on the prognosis of HCC patients was explored by Gene Set Enrichment Analysis (GSEA) enrichment. Results: The expression level of CSNK1D and AFP in cancer foci was significantly higher than that in normal tissues, However, in the same patient, the expression levels of AFP in paracarcinoma tissues and cancer tissues showed no significant difference. The expression level of CSNK1D in HCC with distant metastases was higher than that in those without metastasis, but the expression level of AFP in metastatic HCC was lower than that in those HCC without metastases. In immunohistochemical tests, CSNK1D was moderately positive in normal liver tissues, slightly positive in normal bile duct tissues, and highly positive in HCC. AFP was slightly positive in normal liver tissues and negative in HCC, but it was not detected in normal intrahepatic bile duct tissue. Survival analysis results suggested that the higher expression level of CSNK1D corresponded to the shorter survival period, whereas the expression level of AFP showed no significant influence on survival time. The expression level of CSNK1D was not correlated with gender, age, the status of lymph node metastasis status, or distant metastasis of patients. The main factors influencing the expression level of CSNK1D included tumor size, cancer cell grade, and tumor stage. The expression levels of CSNK1D in T2 and T3 were higher than that in T1. The expression levels of CSNK1D in G3 and G4 were higher than that in G1. The expression levels of CSNK1D in Stage II and Stage III were higher than that in Stage I. Univariate analysis suggested that tumor size, cell grade, distant metastasis, clinical stage, and CSNK1D expression level were the prognostic factors influencing the survival of patients. Multivariate analysis suggested that CSNK1D expression level was an independent factor influencing the prognosis of HCC patients. GSEA enrichment analysis indicated that CSNK1D mainly affected the prognosis of HCC patients through cell cycle, WNT signaling pathway, amino acid degradation metabolism, and other pathways. Conclusion: CSNK1D is an independent influencing factor for the prognosis of HCC patients and has the potential to be developed as a potential therapeutic target for HCC, and better than AFP in predicting the prognosis of HCC.