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Effect of EGCG to multiple myeloma MM.1S cells on gene expression

ABSTRACT: Epigallocatechin-3-gallate (EGCG) is the most plentiful polyphenol in green tea and has antiviral, antioxidant, anti-aging, anti-inflammatory, and neuroprotective effects . Studies have shown that EGCG can inhibit a diversity of biological processes of tumor progression, including cell proliferation, invasion, metastasis, and angiogenesis, and can also induce apoptosis and cell cycle arrest. In order to investigate the role of EGCG in multiple myeloma (MM), we carried out this study. We found that EGCG could inhibit myeloma cell activity and promote myeloma cell apoptosis. To further explore the mechanism of EGCG promoting apoptosis in myeloma cells, cells were treated with EGCG and subjected to RNA sequencing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE256433 | GEO | 2025/02/23

REPOSITORIES: GEO

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Project description:Overexpression of the epidermal growth factor receptor family member Her-2/neu in breast cancer leads to autophosphorylation of the receptor, and induction of multiple downstream signaling pathways including Akt kinase to NF-ï«B cascade that is associated with poor prognosis. Previously, we demonstrated green tea polyhenol epigallocatechin 3-gallate (EGCG) inhibits growth of NF639 Her-2/neu-driven breast cancer cells via reducing receptor autophosphorylation, and downstream Akt and NF-ï«B activities (Pianetti et al., 2002). Interestingly, we noted that upon prolonged culture in the presence of EGCG some cells developed resistance to the polyphenol. Here we report that resistant cells have lost tyrosine phosphorylation on the Her-2/neu receptor. Surprisingly, they displayed elevated NF-ï«B activity, and inhibition of this activity sensitized cells to EGCG. Data from microarray analysis of the original and resistant NF639 populations of cells were subjected to Gene Set Enrichment Analysis (GSEA) pathway analysis, which revealed that the mitogen activated protein kinase (MAPK) pathway was activated in the resistant cells. Treatment of the resistant cells with a combination of EGCG and the MAPK inhibitor U0216 dramatically reduced colony growth and mesenchymal phenotype. Thus, activation of the MAPK pathway mediates resistance to EGCG. Our studies suggest that gene expression profiling of drug resistant cells may provide a mechanism of determining effective systemic therapies for treatment of these advanced cancers. Experiment Overall Design: Total RNA from original NF639 cells and EGCG resistant NF639 cells were harvested using the UltraspecII RNA isolation kit (Biotecx), following the manufacturerâs instruction. The RNA samples were submitted to Boston University Microarray Resource for microarray hybridization using Affymetrix Mouse 430A 2.0 chips. RNAs from two independent experiments were analyzed and data pooled for computational analysis.

Project description:Background: Hepatocellular carcinoma (HCC) is increasing in incidence and treatment is often unsuccessful. Thus, prevention in high-risk patients with established cirrhosis has been proposed as an alternative strategy. It has been suggested that the increased inflammation and fibrogenesis observed during cirrhosis predisposes the liver to future malignant transformation to HCC through a “field effect”. A growing body of evidence indicates that the green tea polyphenol, (-)-epigallocatechin gallate (EGCG), can reduce inflammation and fibrogenesis during chronic liver injury. Here, we test the hypothesis that EGCG administered in the setting of cirrhosis can prevent future HCC development. Methods: A rat model of diethylnitrosamine (DEN)-induced cirrhosis was used to examine the efficacy of EGCG for inhibition of HCC formation in these cirrhotic livers. DEN (50 mg/kg) was administered weekly throughout the study while 0.02% EGCG was given in drinking water beginning at the onset of cirrhosis. At the end of the study, rats were sacrificed, livers were sectioned and stained to analyze disease progression and tumor nodules were counted. Liver function tests were performed to determine liver injury and overall liver function. Finally, genome-wide gene expression profiling on the surrounding, non-tumoral liver tissue was used to monitor the “field effect” in response to EGCG. Results: EGCG significantly (p < 0.01) prevented the development of HCC tumor nodules from on average 18.8 in vehicle controls to on average 9.1 in EGCG-treated animals. EGCG also reduced liver injury and improved liver function as assessed by serum chemistry tests. Finally, a gene expression signature predictive of poor survival and HCC development in human cirrhosis patients was reversed in response to EGCG. Conclusions: Our data are consistent with the growing body of evidence suggesting that EGCG has protective effects in liver disease. Further, our results suggest that EGCG is a potentially effective HCC prevention strategy that can be monitored using gene expression signatures.

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Effect of EGCG to multiple myeloma MM.1S cells on gene expression

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