Epigallocatechin‐3‐gallate induces telomere shortening and clastogenic damage in glioblastoma cells

Abstract

Epigallocatechingallate (EGCG) is the major polyphenol in green tea, to which many anticancer features, such as antioxidative, antigenotoxic, and antiangiogenetic properties, are attributed. Moreover, it is also well known as a telomerase inhibitor. In this work, we have chronically treated U251 glioblastoma cells with low, physiologically realistic concentrations, of EGCG, in order to investigate its effects both on telomeres and on genome integrity. Inhibition of telomerase activity caused telomere shortening, ultimately leading to senescence and telomere dysfunction at 98 days. Remarkably, we have observed DNA damage through an increase of phosphorylation of γ‐H2AX histone and micronuclei also with doses and at timepoints when telomere shortening was not present. Therefore, we concluded that this DNA damage was not correlated with telomere shortening and that EGCG treatment induced not only an increase of telomere‐shortening‐induced senescence but also telomere‐independent genotoxicity. This study questions the common knowledge about EGCG properties, but confirms the few works that indicated the clastogenic properties of this molecule, probably due to DNA reductive damage and topoisomerase II poisoning. Environ. Mol. Mutagen., 60:683–692, 2019. © 2019 Wiley Periodicals, Inc.

Coffee and tea consumption and the risk of glioma: a systematic review and dose–response meta-analysis

“…24,25 The epicatechin-3-gallate and epigallocatechin-3-gallate in tea has antiinflammation, anticarcinogenic, antiproliferative, antioxidant, antifibrosis, and anticollagenase properties. [26][27][28][29] Additionally, epigallocatechin-3-gallate has been reported to reactivate methylation-silenced genes in cancer cells, including MGMT. 13 Higher MGMT activation is postulated to protect against the development of various cancers, including glioma, whereas, the genetic polymorphism of MGMT has been associated with the risk of glioma.…”

“…While the others study evaluates all types of glioma, Nelson et al only evaluate the Various therapeutic effects of polyphenols found in coffee and tea may be helpful against many pathological conditions, including cancer (5,24) . The epicatechin-3-gallate and epigallocatechin-3-gallate in tea have antiinflammation, anticarcinogenic, antiproliferative, antioxidant, antifibrosis and anticollagenase properties (25)(26)(27)(28) . Additionally, epigallocatechin-3-gallate has been reported to reactivate methylation-silenced genes in cancer cells, including O6-methylguanine-DNA methyltransferase (MGMT) (13) .…”

Bioactive Phenolic Compounds in the Modulation of Central and Peripheral Nervous System Cancers: Facts and Misdeeds

“…On the contrary, the addition of EGCG to non-tumor glial cell culture (GliaX) enhances MGMT expression by inhibiting the methylation of the MGMT promoter [107]. Recently, it has been shown that EGCG induces telomere shortening in U251 glioblastoma, leading to senescence [108]. In addition, it also promotes telomere-independent genotoxicity [108].…”

“…Recently, it has been shown that EGCG induces telomere shortening in U251 glioblastoma, leading to senescence [108]. In addition, it also promotes telomere-independent genotoxicity [108].…”

Potential of Naturally Derived Compounds in Telomerase and Telomere Modulation in Skin Senescence and Aging

“…After a 35 day treatment, enhanced hair growth was noted among C57BL/6 mice [151]. Studies have shown that polyphenols augment mTERT and β-catenin gene expression levels in the dorsal skin cells of mice as well as in the human keratinocyte cell line HaCaT [152]. Considering the fact that hTERT is only selectively expressed in skin cells (see Table 2), naturally derived compounds might also selectively but efficiently substitute or supplement the hTERT-mediated anti-aging mechanisms.…”