The green tea polyphenol EGCG is differentially associated with telomeric regulation in normal human fibroblasts versus cancer cells

Abstract

Introduction: Topical investigations have demonstrated that oxidative stress and inflammation play key roles in biological aging and determine incidence and course of age-related diseases. Lifestyle and environmental factors hugely impact epigenetic regulation and DNA stability with telomere attrition and epigenetic instability providing a potential record of the cumulative burden of endogenous and exogenous oxidative noxae. Certain physiologically active plant components exhibit antioxidative activities affecting epigenetic regulation of inflammation response and DNA repair.Methods: Against this background, the present study investigated green tea polyphenol epigallocatechin gallate (EGCG) in the context of telomere regulation in Caco-2 colorectal adenocarcinoma cells vs. ES-1 primary skin fibroblasts. Cell lines were treated with 20 and 200 µM EGCG for 36, 72 and 144 hours, respectively. Telomerase activity, relative telomere length as well as methylation status of hTERT and c-Myc from different culture conditions were assessed. Malondialdehyde (MDA) served as a surrogate marker of potential pro-oxidative effects of EGCG in a physiologically relevant tissue model.Results: EGCG incubation was associated with telomere shortening and decreased telomerase activity in Caco-2 cells, and relatively longer telomeres along with increased methylation of six 5'—C—phosphate—G—3' (CpG) sites in the promoter region of human Telomerase Reverse Transcriptase (hTERT) in fibroblasts. At low concentrations, EGCG significantly decreased oxidative damage to lipids in Caco-2 cells and attenuated H2O2 induced oxidation at higher concentrations.Conclusion: These results suggest differential EGCG-mediated telomeric modulation in cancer vs. primary cells and a specific antioxidant activity of EGCG against oxidative damage to lipids in abnormal cells.Keywords: Caco-2, epigallocatechin gallate, telomeres, hTERT, DNA methylation, telomerase, oxidative stress, malondialdehyde

Pycnogenol - extract from French maritime pine bark (Pinus pinaster), as an effective antioxidant against superoxide radical

“…uric acid, glutathione), while others are ingested through the diet. Exogenous antioxidants, including polyphenols and their derivatives, are well described in the scientific literature [23]. The number and position of hydroxyl groups in the molecule determine their antioxidant activity.…”

Targeting Cancer Hallmarks with Epigallocatechin Gallate (EGCG): Mechanistic Basis and Therapeutic Targets

“…On the other hand, relatively longer telomeres along with increased methylation were observed in fibroblasts after treatment with EGCG. Also, antioxidant activity was reported at 20 and 200 µM [ 50 ]. Furthermore, it was detected that EGCG can bargain some protection against UV-induced DNA damage in cell cultures and human peripheral blood samples [ 51 ].…”

“…The effects of EGCG on telomerase activity were observed in several cancer models. It was reported that 20 and 200 µM of EGCG caused telomere shortening and decreased telomerase activity in Caco-2 cells [ 50 ]. Moreover, in glioblastoma, EGCG suppressed the growth of U251 cells through telomerase inhibition [ 106 ].…”

Cell Survival, Death, and Proliferation in Senescent and Cancer Cells: the Role of (Poly)phenols

“…Methylation of c-Myc is considered an indirect mechanism used to regulate telomerase through hTERT. In fact, it has been observed that c-Myc methylation is significantly higher in some tumor cell lines after treatment with EGCG [ 193 ]. The methylation status of hTERT was, in some cancer cell lines such as Caco-2 cells, little affected by EGCG treatment [ 193 ].…”

“…In fact, it has been observed that c-Myc methylation is significantly higher in some tumor cell lines after treatment with EGCG [ 193 ]. The methylation status of hTERT was, in some cancer cell lines such as Caco-2 cells, little affected by EGCG treatment [ 193 ]. Conversely, in other tumor cell lines, such as HeLa cells (cervical tumor cell line) a significant decrease in telomere length and decreased telomerase activity was observed after treatment with EGCG [ 182 ].…”