Juglanthraquinone C Induces Intracellular ROS Increase and Apoptosis by Activating the Akt/Foxo Signal Pathway in HCC Cells

Hou, Yaqin; Yao, Yao; Bao, Yongli; Song, Zhenbo; Yang, Cheng; Xiuli, Gao; Zhang, Wenjing; Sun, Luguo; Yu, Chunlei; Huang, Yanxin; Wang, Guan‐Nan; Li, Yuxin

doi:10.1155/2016/4941623

Cited by 41 publications

(28 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The forkhead box O1 (Foxo) signaling pathway participates in the regulation of multiple biological processes, including cellular responses to oxidative stress, cellular apoptosis and cell proliferation (31)(32)(33). It was reported that juglanthraquinone C could induce the apoptosis of HCC cells by activating the Foxo signaling pathway (34). PS341 (Bortezomib) was the first proteasome-inhibitor drug to be approved in clinical treatment for multiple myeloma, functioning by mediating targeted therapy against HCC through the Foxo3 signaling pathway (35).…”

Section: Discussionmentioning

confidence: 99%

Potential biomarkers of HCC based on gene expression and DNA methylation profiles

2018

View full text Add to dashboard Cite

The aim of the present study was to identify potential biomarkers of hepatocellular carcinoma (HCC). Three gene expression profiles of GSE95698, GSE49515 and GSE76427 and a DNA methylation profile of GSE73003 were downloaded from the Gene Expression Omnibus (GEO) database, each comprising data regarding HCC and control tissue samples. The differentially expressed genes (DEGs) between the HCC group and the control group were identified using the limma software package. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the overlapping DEGs. The PPI network of the overlapping DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins. A total of 41 DEGs were identified in HCC the group compared with control group. The overlapping DEGs were enriched in 11 GO terms and 3 KEGG pathways. A total of 6,349 DMSs were identified, and 6 of the differentially expressed genes were also differentially methylated [Denticleless protein homolog (), Dual specificity phosphatase 1 (), Eomesodermin, Endothelial cell specific molecule 1, Nuclear factor κ-light-chain gene enhancer of activated B cells inhibitor, α (NFKBIA) and suppressor of cytokine signaling 2 ()]. The present study suggested that and may be potential biomarkers of HCC, and the tumor protein 'p53 signaling', 'forkhead box O1' signaling and 'metabolic' pathways may serve roles in the pathogenesis of HCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Potential biomarkers of HCC based on gene expression and DNA methylation profiles

2018

View full text Add to dashboard Cite

show abstract

“…FOXO is an important transcription factor that determines cell fate and is associated with a broad range of cellular physiological functions, such as differentiation, apoptosis, cell proliferation, DNA damage and repair and mediating oxidative stress among a wide range of cancers (83,84). The intracellularly initiation pathway of apoptosis induced by the FOXO protein is associated with oxidative stress, which occurs when ROS is released into the cytoplasm (85). The FOXO1 and FOXO3a transcription factors typically actived during oxidative stress causing apoptotic cell injury (86,87).…”

Section: Discussionmentioning

confidence: 99%

Effect of simulated microgravity on metabolism of HGC‑27 gastric cancer cells

et al. 2020

View full text Add to dashboard Cite

The understanding into the pathogenesis and treatment of gastric cancer has improved in recent years; however, a number of limitations have delayed the development of effective treatment. Cancer cells can undergo glycolysis and inhibit oxidative phosphorylation in the presence of oxygen (Warburg effect). Previous studies have demonstrated that a rotary cell culture system (RCCS) can induce glycolytic metabolism. In addition, the potential of regulating cancer cells by targeting their metabolites has led to the rapid development of metabolomics. In the present study, human HGC-27 gastric cancer cells were cultured in a RCCS bioreactor, simulating weightlessness. Subsequently, liquid chromatography-mass spectrometry was used to examine the effects of simulated microgravity (SMG) on the metabolism of HGC-27 cells. A total of 67 differentially regulated metabolites were identified, including upregulated and downregulated metabolites. Compared with the normal gravity group, phosphatidyl ethanolamine, phosphatidyl choline, arachidonic acid and sphinganine were significantly upregulated in SMG conditions, whereas sphingomyelin, phosphatidyl serine, phosphatidic acid, L-proline, creatine, pantothenic acid, oxidized glutathione, adenosine diphosphate and adenosine triphosphate were significantly downregulated. The Human Metabolome Database compound analysis revealed that lipids and lipid-like metabolites were primarily affected in an SMG environment in the present study. Overall, the findings of the present study may aid our understanding of gastric cancer by identifying the underlying mechanisms of metabolism of the disease under SMG.

show abstract

“…Notably, the PI3K/Akt signaling pathway is associated with LIHC progression, vascular infiltration and metastasis, as well as poor prognosis and a low survival rate in patients with LIHC ( 20 ). Furthermore, the FoxO signaling pathway, which is closely associated with the PI3K/Akt signaling pathway, serves an important role in the occurrence and development of hepatocellular carcinoma ( 21 , 22 ).…”

Section: Introductionmentioning

confidence: 99%

Effect of let‑7c on the PI3K/Akt/FoxO signaling pathway in hepatocellular carcinoma

Wang

2020

Oncol Lett

View full text Add to dashboard Cite

The early diagnosis and treatment of liver hepatocellular carcinoma (LIHC) remains a major challenge. Therefore, it is of great significance to strengthen basic research on LIHC in order to improve the prevention and treatment of the disease. Numerous studies have indicated that the PI3K/Akt and FoxO signaling pathways mediate proliferation, survival and migration during the development of LIHC. Therefore, they have become a target for LIHC treatment. Furthermore, let-7c has been demonstrated to repress cell proliferation, migration and invasion, and to induce G 1 phase arrest and apoptosis of LIHC cells. However, the mechanism of its action is not clear. In the present study, the association between let-7c and the PI3K/Akt/FoxO signaling pathway, as well as their roles in the development of LIHC were investigated using The Cancer Genome Atlas and various public databases (Tumor-miRNA-Pathway, OncomiR, DIANA-TarBase v8, KOBAS 3.0, ONCOMINE, Kaplan-Meier plotter, LinkedOmics, UALCAN and cBioPortal). The effects of let-7c-5p on PI3K/Akt/FoxO signaling pathway-related target genes were analyzed following overexpression of let-7c-5p in the MHCC-97H cell line via reverse transcription-quantitative PCR, and the let-7c-5p target genes belonging to the PI3K/Akt/FOXO signaling pathway in LIHC were screened out. GO and KEGG enrichment analyses of these target genes was performed using g:Profiler, gOST. In addition, GeneMANIA and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) databases were used to determine the gene-gene and protein-protein interaction networks, respectively. The data demonstrated that cyclin B2 (CCNB2), cyclin E2 (CCNE2), cyclin dependent kinase 4 (CDK4), homer scaffold protein 1 (HOMER1), heat shock protein 90 α family class A member 1 (HSP90AA1), neuroblastoma RAS viral oncogene homolog (NRAS), protein phosphatase 2 catalytic subunit α (PPP2CA), protein kinase AMP-activated catalytic subunit α2 (PRKAA2) and Rac family small GTPase 1 (RAC1) may be target genes of let-7c-5p. These genes, particularly CCNE2, were associated with poor overall survival and could be promising candidate biomarkers for disease and poor prognosis in LIHC. Among them, seven genes (CCNE2, CDK4, HSP90AA1, NRAS, PPP2CA, PRKAA2 and RAC1) belonged to the PI3K-Akt signaling pathway and four genes (CCNB2, HOMER1, NRAS and PRKAA2) belonged to the FoxO signaling pathway. The majority of these genes were closely associated with the cell cycle and their elevated expression may aggravate cell cycle disorders. Therefore, let-7c may be considered to be an anti-oncogene of LIHC. The present study may provide novel targets and strategies for the diagnosis and treatment of LIHC.

show abstract

Juglanthraquinone C Induces Intracellular ROS Increase and Apoptosis by Activating the Akt/Foxo Signal Pathway in HCC Cells

Cited by 41 publications

References 51 publications

Potential biomarkers of HCC based on gene expression and DNA methylation profiles

Potential biomarkers of HCC based on gene expression and DNA methylation profiles

Effect of simulated microgravity on metabolism of HGC‑27 gastric cancer cells

Effect of let‑7c on the PI3K/Akt/FoxO signaling pathway in hepatocellular carcinoma

Contact Info

Product

Resources

About