Browse
Submit Data
Databases
API
Help

Dataset Information

20 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Podofilox suppresses gastric cancer cell proliferation by regulating cell cycle arrest and the c-Myc/ATG10 axis.

ABSTRACT: Gastric cancer (GC) is a malignancy for which effective therapeutic drugs are limited. Podofilox exhibits antitumor effects in various types of cancer; however, whether it may inhibit GC growth remains unknown. The aim of the present study was to investigate the role of podofilox in GC. Cell Counting Kit-8, colony formation and cell cycle assays were used to detect the role of podofilox on cellular proliferation and the cell cycle, respectively. A microarray was used to detect the transcriptional changes induced by podofilox in GC cells. The results of the present study demonstrated that podofilox inhibited GC cell proliferation and colony formation. The half maximal inhibitory concentration of podofilox in AGS and HGC-27 cells was 2.327 and 1.981 nM, respectively. In addition, treatment with podofilox induced G₀/G₁ cell cycle arrest. Molecular analysis based on microarray data demonstrated that podofilox altered the expression levels of genes involved in the cell cycle, c-Myc and p53 signaling. Autophagy-related 10 (ATG10), which was highly expressed in GC tissues, was also downregulated by podofilox, as demonstrated by the results of the microarray analysis and immunoblotting. To determine the involvement of ATG10 in GC, ATG10 was knocked down in GC cells by small interfering RNA, which suppressed the proliferation and colony formation of GC cells compared with those observed in the control-transfected cells. Taken together, the results of the present study suggested that podofilox may inhibit GC cell proliferation by preventing the cell cycle progression and regulating the c-Myc/ATG10 signaling pathway.

SUBMITTER: An J

PROVIDER: S-EPMC8422391 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

COPB2 suppresses cell proliferation and induces cell cycle arrest in human colon cancer by regulating cell cycle-related proteins.

Project description:Coat proteins (COPs), including the major types clathrin, COPI and COPII, play a considerable role in intracellular transport by initiating the formation of transport vesicles. Coatomer protein complex subunit ?2 (COPB2) is one of the seven subunits that make up a COPI complex. In the present study, we found that COPB2 was highly expressed in human colon cancer specimens. However, to date, there have been no reports describing the functions of COPB2 in human colon cancer cells. In this study, we analyzed the functions of COPB2 in the proliferation and cell cycle arrest of human RKO and HCT116 colon cancer cells by using lentivirus-mediated RNAi infection. Our results demonstrated that the silencing of COPB2 in vitro could inhibit the proliferation and colony formation abilities of RKO and HCT116 cells. Furthermore, measurement of cell cycle distribution indicated that the downregulation of COPB2 could induce G0/G1 or S phase cell cycle arrest by regulating cell cycle-related proteins. In conclusion, our results suggest that COPB2 plays a key role in the proliferation and cell cycle progression of human RKO and HCT116 colon cancer cells, thus indicating that COPB2 might be a potential therapeutic target for the treatment of human colon cancer.

| S-EPMC5772868 | biostudies-literature

Downregulation of SOX9 suppresses breast cancer cell proliferation and migration by regulating apoptosis and cell cycle arrest.

Project description:SRY-related high-mobility group box 9 (SOX9) is an important transcriptional factor that regulates diverse genes involved in development and stemness. Dysregulation of SOX9 encourages carcinogenesis in various types of cancer, including breast cancer. The present study aimed to explore the role of SOX9 in triple-negative breast cancer (TNBC). SOX9 expression was significantly upregulated in the TNBC MDA-MB-231, MDA-MB-436 and MDA-MB-468 cell lines compared with that in BT-549 cells. Based on a lentivirus assay, SOX9 inhibition in MDA-MB-231 and MDA-MB-436 cells suppressed cell proliferation and colony formation. Apoptosis was increased and the cell cycle was arrested at the G0/G1 phase in SOX9-knockdown cells. Transwell and wound-healing assays demonstrated that SOX9 inhibition decreased the migration and invasion of MDA-MB-231 and MDA-MB-436 cells. RNA sequencing identified that numerous genes were regulated by SOX9, including nucleophosmin, thioredoxin reductase 1, succinate dehydrogenase complex subunit D, nuclear receptor binding SET domain protein 2, eukaryotic translation initiation factor 4γ1 and glycogen phosphorylase L. Overall, the current study suggested that SOX9 acted as an oncogene in TNBC.

| S-EPMC8114479 | biostudies-literature

Dual EZH2 and G9a inhibition suppresses multiple myeloma cell proliferation by regulating the interferon signal and IRF4-MYC axis.

Project description:Epigenetic mechanisms such as histone modification play key roles in the pathogenesis of multiple myeloma (MM). We previously showed that EZH2, a histone H3 lysine 27 (H3K27) methyltransferase, and G9, a H3K9 methyltransferase, are potential therapeutic targets in MM. Moreover, recent studies suggest EZH2 and G9a cooperate to regulate gene expression. We therefore evaluated the antitumor effect of dual EZH2 and G9a inhibition in MM. A combination of an EZH2 inhibitor and a G9a inhibitor strongly suppressed MM cell proliferation in vitro by inducing cell cycle arrest and apoptosis. Dual EZH2/G9a inhibition also suppressed xenograft formation by MM cells in vivo. In datasets from the Gene Expression Omnibus, higher EZH2 and EHMT2 (encoding G9a) expression was significantly associated with poorer prognoses in MM patients. Microarray analysis revealed that EZH2/G9a inhibition significantly upregulated interferon (IFN)-stimulated genes and suppressed IRF4-MYC axis genes in MM cells. Notably, dual EZH2/G9a inhibition reduced H3K27/H3K9 methylation levels in MM cells and increased expression of endogenous retrovirus (ERV) genes, which suggests that activation of ERV genes may induce the IFN response. These results suggest that dual targeting of EZH2 and G9a may be an effective therapeutic strategy for MM.

| S-EPMC7803977 | biostudies-literature

Huaier n-butanol extract suppresses proliferation and metastasis of gastric cancer via c-Myc-Bmi1 axis.

Project description:Gastric cancer (GC) ranks as the third leading cause of cancer-related mortality worldwide, and approximately 42% of all cases diagnosed each year worldwide are diagnosed in China. A large number of clinical applications have revealed that Trametes robiniophila ?urr. (Huaier) exhibits an anti-tumour effect. However, loss of the bioactive components of Huaier during the extraction procedure with water is unavoidable, and the underlying mechanism of the anti-cancer effect of Huaier remains poorly understood. In this study, we investigated the anti-cancer effect of Huaier n-butanol extract, which contained 51.4% total flavonoids, on HGC27, MGC803, and AGS human GC cell lines in vitro. At a low concentration, Huaier n-butanol extract inhibited the growth of these GC cell types, induced cell cycle arrest and reduced cell metastasis. Moreover, Huaier n-butanol extract suppressed the c-Myc-Bmi1 signalling pathway, and overexpression of Bmi1 reversed the effects of Huaier n-butanol extract on GC cells. Thus, our findings indicate that Huaier n-butanol extract suppresses the proliferation and metastasis of GC cells via a c-Myc-Bmi1-mediated approach, providing a new perspective for our understanding of the anti-tumour effects of Huaier. These results suggest that Huaier n-butanol extract could be an attractive therapeutic adjuvant for the treatment of human GC.

| S-EPMC6346047 | biostudies-literature

REG γ knockdown suppresses proliferation by inducing apoptosis and cell cycle arrest in osteosarcoma.

Project description:BackgroundOsteosarcoma (OS) is the most common malignant bone tumor with high mortality in children and adolescents. REG γ is overexpressed and plays oncogenic roles in various types of human cancers. However, the expression and potential roles of REG γ in osteosarcoma are elusive. This study aims at exploring possible biological functions of REG γ in the pathogenesis of osteosarcoma and its underlying mechanism.MethodsQuantitativereverse transcription-polymerase chain reaction (qRT-PCR), western blotting andimmunohistochemistry (IHC)were performed to detect the expression levels of REG γ in OS tissues and cell lines. Then, the effects of REG γ expression on OS cell proliferation in vitro were analyzed by Cell Counting Kit-8 (CCK-8), ethylene deoxyuridine (EdU), colony formation, flow cytometry. The protein levels of apoptosis and cell-cycle related proteins were evaluated using western blotting.ResultsIn present study, we found for the first time that REG γ is overexpressed in osteosarcoma tissues and cell lines and knockdown of REG γ significantly inhibits cell proliferation and induces apoptosis and cell cycle arrest in osteosarcoma cells. Furthermore, we observed that p21, caspase-3 and cleaved caspase-3 are increased while the expression of cycinD1 and bcl-2 are decreased after REG γ depletion in osteosarcoma cells. In conclusion, REG γ may be involved in the proliferation of osteosarcoma and serve as a novel therapeutic target in patients with osteosarcoma.

| S-EPMC7166046 | biostudies-literature

Piperlongumine Suppresses Proliferation of Human Oral Squamous Cell Carcinoma through Cell Cycle Arrest, Apoptosis and Senescence.

Project description:Oral squamous cell carcinoma (OSCC), an aggressive cancer originating in the oral cavity, is one of the leading causes of cancer deaths in males worldwide. This study investigated the antitumor activity and mechanisms of piperlongumine (PL), a natural compound isolated from Piper longum L., in human OSCC cells. The effects of PL on cell proliferation, the cell cycle, apoptosis, senescence and reactive oxygen species (ROS) levels in human OSCC cells were investigated. PL effectively inhibited cell growth, caused cell cycle arrest and induced apoptosis and senescence in OSCC cells. Moreover, PL-mediated anti-human OSCC behavior was inhibited by an ROS scavenger N-acetyl-l-cysteine (NAC) treatment, suggesting that regulation of ROS was involved in the mechanism of the anticancer activity of PL. These findings suggest that PL suppresses tumor growth by regulating the cell cycle and inducing apoptosis and senescence and is a potential chemotherapy agent for human OSCC cells.

| S-EPMC4849064 | biostudies-literature

Carbonic anhydrase IV inhibits cell proliferation in gastric cancer by regulating the cell cycle.

Project description:Carbonic anhydrase IV (CA4) is silenced in colorectal cancer. However, the effect of CA4 on the development of gastric cancer (GC) is poorly understood. The present study aimed to determine the role of CA4 in GC tumorigenesis and its underlying molecular mechanism. The levels of CA4 in GC cells and tissues were evaluated by reverse transcription-quantitative PCR and immunohistochemistry. CA4 expression was suppressed in GC cells and tissues compared with adjacent healthy tissues and normal human gastric epithelial cells, respectively. This reduced expression was significantly associated with tumor size, invasion and differentiation. Analyses with a real-time cell analyzer and clonogenic assays were conducted to validate the impact of CA4 on GC cell lines (AGS and HGC-27) and normal human gastric epithelial cell line (GES-1) proliferation. The effects of CA4 on the cell cycle in GC cells were determined by flow cytometry. The levels of CA4 and cell cycle-associated proteins were confirmed by western blotting. CA4 overexpression inhibited GC cell proliferation and reduced colony-forming ability, arrested the cell cycle in the G2/M phase, inhibited cyclin B1 and cyclin-dependent kinase 2 expression and induced p21 expression. These results indicate that CA4 may serve an important role in GC tumorigenesis by inhibiting cellular proliferation via regulating the expression of cell cycle-associated proteins. CA4 may serve as a diagnostic biomarker and a potential therapeutic target in GC.

| S-EPMC7405342 | biostudies-literature

Overexpression of SIRT4 inhibits the proliferation of gastric cancer cells through cell cycle arrest.

Project description:The sirtuins (SIRTs) are a family of nicotinamide-adenine dinucleotide (NAD)+-dependent protein deacetylases. SIRT4 is a mitochondrial NAD+-dependent adenosine diphsophate-ribosyltransferase. Recent studies demonstrated that SIRT4 can regulate glutamine metabolism and thus act as a tumor suppressor. However, the association of SIRT4 with gastric cancer remains unknown. The present study investigated the potential role of SIRT4 in the proliferation of human gastric cancer cells. Gastric cancer cell lines (SGC-7901 and MNK45) overexpressing SIRT4 were established by lentiviral infection. The effect of overexpression of SIRT4 in gastric cancer was evaluated by determining the cell viability, proliferation activity and colony-forming ability of gastric cancer cells in vitro. Furthermore, the cell cycle profiles of SGC-7901 and MNK45 cells overexpressing SIRT4 were evaluated to provide insights into potential underlying molecular mechanisms. Overexpression of SIRT4 significantly inhibited the proliferation and colony-forming ability of the gastric cancer cells in vitro. Furthermore, overexpression of SIRT4 induced G1 cell cycle arrest via suppression of phosphorylated extracellular signal-regulated kinase, cyclin D and cyclin E. In conclusion, the results of the present study indicated that SIRT4 may function as a tumor suppressor in gastric cancer by regulating cell proliferation, therefore SIRT4 may be a potential therapeutic target against this disease.

| S-EPMC6350193 | biostudies-literature

Irisin Suppresses Nicotine-Mediated Atherosclerosis by Attenuating Endothelial Cell Migration, Proliferation, Cell Cycle Arrest, and Cell Senescence.

Project description:Atherosclerotic disease has become the major cause of death worldwide. Smoking, as a widespread independent risk factor, further strengthens the health burden of atherosclerosis. Irisin is a cytokine that increases after physical activity and shows an atheroprotective effect, while its specific mechanism in the process of atherosclerosis is little known. The reversal effect of irisin on intimal thickening induced by smoking-mediated atherosclerosis was identified in Apoe -/- mice through the integrin αVβ5 receptor. Endothelial cells treated with nicotine and irisin were further subjected to RNA-seq for further illustrating the potential mechanism of irisin in atherosclerosis, as well as the wound healing assays, CCK-8 assays, β-gal staining and cell cycle determination to confirm phenotypic alterations. Endothelial differential expressed gene enrichment showed focal adhesion for migration and proliferation, as well as the P53 signaling pathway for cell senescence and cell cycle control. Irisin exerts antagonistic effects on nicotine-mediated migration and proliferation via the integrin αVβ5/PI3K pathway. In addition, irisin inhibits nicotine-mediated endothelial senescence and cell cycle arrest in G0/G1 phase via P53/P21 pathway. This study further illustrates the molecular mechanism of irisin in atherosclerosis and stresses its potential as an anti-atherosclerotic therapy.

| S-EPMC9023791 | biostudies-literature