Epicatechin Gallate Impairs Colon Cancer Cell Metabolic Productivity

Abstract

Green tea and grape phenolics inhibit cancer growth and modulate cellular metabolism. Targeting the tumor metabolic profile is a novel therapeutic approach to inhibit cancer cell proliferation. Therefore, we treated human colon adenocarcinoma HT29 cells with the phenolic compound epicatechin gallate (ECG), one of the main catechins in green tea and the most important catechin in grape extracts, and evaluated its antiproliferation effects. ECG reduced tumor viability and induced apoptosis, necrosis, and S phase arrest in HT29 cells. Later, biochemical determinations combined with mass isotopomer distribution analysis using [1,2-(13)C2]-D-glucose as a tracer were used to characterize the metabolic network of HT29 cells in response to different concentrations of ECG. Glucose consumption was importantly decreased after ECG treatment. Moreover, metabolization of [1,2-(13)C2]-D-glucose indicated that the de novo synthesis of fatty acids and the pentose phosphate pathway were reduced in ECG-treated cells. Interestingly, ECG inhibited the activity of transketolase and glucose-6-phosphate dehydrogenase, the key enzymes of the pentose phosphate pathway. Our data point to ECG as a promising chemotherapeutic agent for the treatment of colon cancer.

Metabolic consequences of LDHA inhibition by epigallocatechin gallate and oxamate in MIA PaCa-2 pancreatic cancer cells

“…Using tracer-based metabolomics we showed that LDHA activity was reduced by ECGC through the inhibition of LDHA expression, and by oxamate through the direct inhibition of LDHA enzyme. Our findings of indirect and direct action of ECGC and oxamate on lactate production in cancer cells are consistent with previous reported observations in breast cancer cells (Thornburg et al , 2008) and colon cancer cells (Sanchez-Tena et al , 2013). The change in LDHA activity directly impaired the flux balance through the pyruvate pool and provoked a systems response throughout the metabolic network to achieve a new state of substrate balance and homeostasis.…”

Cytotoxic and Immunomodulatory Potential Activity of Physalis peruviana Fruit Extracts on Cervical Cancer (HeLa) and Fibroblast (L929) Cells

“… 29 Epicatechin gallate was only found in isopropanol extracts, which in green tea has been associated with tumor viability reduction and apoptosis induction in human colon adenocarcinoma cells (HT29). 30 Another study reported the presence of rutin, kaempferol, myricetin, and quercetin in a phytochemical screening (HPLC, Fourier transform infrared mass spectrometry) for Indian fruits of Physalis peruviana 31 ; none of these were found in this current study. The variation of polyphenolic composition depends on many factors, including among others, varietals, ripening stage, climate variations, and the progressive binding to the cell walls, as a defense mechanism against pathogen and stress factors.…”

Metabolomics approaches in pancreatic adenocarcinoma: tumor metabolism profiling predicts clinical outcome of patients

“…Elevated expression of lactate dehydrogenase A (LDHA) is highlighted in breast and colorectal cancers [39, 40] and has been recently identified in pancreatic cancers [41]. Some studies have already shown the different steps where LDHA is involved (tumor initiation, maintenance, and progression) [42, 43].…”