Effects of Epigallocatechin Gallate (EGCG) on Urinary Bladder Urothelial Carcinoma―Next-Generation Sequencing and Bioinformatics Approaches

Abstract

Background and objectives: Bladder urothelial carcinoma is the most common type of genitourinary cancer. Patients with bladder cancer may have limited treatment efficacy related to drug toxicity, resistance or adverse effects, and novel therapeutic strategies to enhance treatment efficacy or increase sensitivity to drugs are of high clinical importance. Epigallocatechin gallate (EGCG) is a polyphenolic compound found in green tea leaves, and a potential anti-cancer agent in various cancer types through modulating and regulating multiple signaling pathways. The current study aimed to explore the role and novel therapeutic targets of EGCG on bladder urothelial carcinoma. Materials and Methods: The BFTC-905 cells, human urinary bladder transitional cell carcinoma (TCC) cell line, were treated with EGCG or water for 24 hours, and the expression profiles of mRNAs and microRNAs were analyzed using next generation sequencing (NGS). The enriched biological functions were determined using different bioinformatics databases. Results: A total of 108 differentially expressed genes in EGCG-treated bladder TCC cells were identified, which were mainly involved in nicotinamide adenine dinucleotide (NAD) biogenesis, inflammatory response and oxidation-reduction metabolism. Moreover, several microRNA-mRNA interactions that potentially participated in the response of bladder TCC to EGCG treatment, including miR-185-3p-ARRB1 (arrestin beta 1), miR-3116-MGAT5B (alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase B), miR-31-5p-TNS1 (tensin 1), miR-642a-5p-TNS1, miR-1226-3p-DLG2 (discs large homolog 2), miR-484-DLG2, and miR-22-3p-PPM1K (protein phosphatase 1K). Conclusions: The current findings provide insights into novel therapeutic targets and underlying mechanisms of action of EGCG treatment in bladder cancer.

Polyphenols in cancer prevention: New insights (Review)

“…An in vitro study conducted on BFTC-905 cells, a human urinary bladder transitional cell carcinoma (TCC) cell, treated with EGCG, identified 108 differentially expressed genes and 22 candidate genes with potential miRNA interactions. These genes were mainly involved in the biogenesis of nicotinamide adenine dinucleotide (NAD), in the inflammatory response and in the oxidation-reduction metabolism (58). CUR is capable of suppressing the growth of a variety of cancer cells, including those of bladder cancer.…”

The Importance of Reporting Clinical and Epidemiological Data in Urology: Local Experiences and Insights from the International Literature

“…Lee et al studied the potential anticancer properties of epigallocatechin gallate (EGCG) on a human urinary bladder transitional cell carcinoma (TCC) cell line; during the analyses, the expression profiles of mRNAs and microRNAs were analyzed using next-generation sequencing (NGS) and bioinformatics. Overall, they identified several differentially expressed genes in response to EGCG treatment, notably those involved in redox-metabolism, inflammatory response, and nicotinamide adenine dinucleotide (NAD) biogenesis, which may all have important roles in the persistence of malignant cells [37]. Anglickis et al compared the efficacy of microwave thermal ablation (MWT) with open partial nephrectomy (OPN) in the treatment of small renal tumors patients over 70 years old in the period between January 2012 and January 2019 in Lithuania.…”

Natural Phytochemicals in Bladder Cancer Prevention and Therapy

“…The genes upregulated by EGCG include general transcription factor IIH subunit 2 family member C (GTF2H2C), proline rich transmembrane protein 2 (PRRT2), RAS p21 protein activator 4 (RASA4), transmembrane protein 92 (TMEM92), and RANBP2 like and GRIP domain containing 5 (RGPD5), whereas those downregulated include kynurenine 3-monooxygenase (KMO), NADH: ubiquinone oxidoreductase core subunit S1 (NDUFS1), gastric inhibitory polypeptide receptor (GIPR), and thioredoxin domain containing 2 (TXNDC2). Furthermore, many miRNA-mRNA interactions that mediate the response to EGCG treatment have been identified, including miR-22-3p-protein phosphatase 1K (miR-22-3p-PPM1K), miR-31-5p-tensin 1 (miR-31-5p-TNS1), and miR-185-3p-arrestin beta 1 (miR-185-3p-ARRB1) (42). Recently, a double-blind, randomized, clinical trial was performed in presurgical bladder cancer patients.…”