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Integrated transcriptomic and metabolomic analyses to characterize the anti-cancer effects of (-)-epigallocatechin-3-gallate in human colon cancer cells.

Abstract：

:(-)-Epigallocatechin-3-gallate (EGCG) is the main bioactive component in tea (Camellia sinensis) catechins, and exhibits potential antitumor activity against colorectal cancer (CRC). However, the underlying mechanisms are largely unclear. We investigated the effects of EGCG on activities of CRC cells and the exact molecular mechanism. We used human colon cancer cells (HT-29) and exposed them to EGCG at various concentrations. The MTT assay, flow cytometry, and TUNEL staining were used to study the underlying mechanisms of EGCG (proliferation, apoptosis, autophagy). Western blotting was used to measure expression of marker proteins of the cell cycle, apoptosis, and autophagy. Using a combined microarray-based transcriptomic and ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UHPLC-QTOF/MS)-based metabolomic approach, we investigated the perturbed pathways induced by EGCG treatment at transcript and metabolite levels. Transcriptomic analyses showed that 486 genes were differentially expressed between untreated and EGCG-treated cells. Also, 88 differentially expressed metabolites were identified between untreated and EGCG-treated cells. The altered metabolites were involved in the metabolism of glutathione, glycerophospholipids, starch, sucrose, amino sugars, and nucleotide sugars. There was substantial agreement between the results of transcriptomics and metabolomics analyses. Our data indicate that the anticancer activity of EGCG against HT-29 cells is mediated by induction of cell-cycle arrest, apoptosis, and autophagy. EGCG modulates cancer-cell metabolic pathways. These results provide a platform for future molecular mechanistic studies of EGCG.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Zhang Z,Zhang S,Yang J,Yi P,Xu P,Yi M,Peng W

doi

10.1016/j.taap.2020.115100

subject

Has Abstract

pub_date

2020-08-15 00:00:00

pages

115100

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(20)30224-6

journal_volume

401

pub_type

杂志文章

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Integrated transcriptomic and metabolomic analyses to characterize the anti-cancer effects of (-)-epigallocatechin-3-gallate in human colon cancer cells.