Modulation of Telomerase Activity in Cancer Cells by Dietary Compounds: A Review

Abstract

Telomerase is expressed in ~90% of human cancer cell lines and tumor specimens, whereas its enzymatic activity is not detectable in most human somatic cells, suggesting that telomerase represents a highly attractive target for selective cancer treatment. Accordingly, various classes of telomerase inhibitors have been screened and developed in recent years. We and other researchers have successfully found that some dietary compounds can modulate telomerase activity in cancer cells. Telomerase inhibitors derived from food are subdivided into two groups: one group directly blocks the enzymatic activity of telomerase (e.g., catechin and sulfoquinovosyldiacylglycerol), and the other downregulates the expression of human telomerase reverse transcriptase (hTERT), the catalytic subunit of human telomerase, via signal transduction pathways (e.g., retinoic acid and tocotrienol). In contrast, a few dietary components, including genistein and glycated lipid, induce cellular telomerase activity in several types of cancer cells, suggesting that they may be involved in tumor progression. This review summarizes the current knowledge about the effects of dietary factors on telomerase regulation in cancer cells and discusses their molecular mechanisms of action.

TheSaccharomyces cerevisiaeHrq1 and Pif1 DNA helicases synergistically modulate telomerase activityin vitro

“…Hrq1 also caused a stalling event at T25, but this effect was weaker than that observed with Pif1 ( Fig. 3A lanes [5][6][7][8]. Unlike Pif1, however, Hrq1 caused an increase in the amount of signal (i.e., decreased processivity) at positions T28 and T30 (Fig.…”

“…For instance, the transcription of human TERT can be altered genetically and epigenetically in cancers, leading to upregulation of telomerase activity (5). Similarly, the transcription of genes encoding telomerase components and telomerase activity itself can be up-or downregulated by various dietary compounds (6). Post-translational modifications of TERT, such as phosphorylation (7) and ubiquitination (8), also affect telomerase activity.…”

Vitamin E: Regulatory Redox Interactions

“…As this vitamin E family cannot be synthesized in the human body, these nutrients must be supplied exogenously through diet. Recent discoveries have indicated that vitamin E exhibits various potentially beneficial effects on human health, such as anti‐allergic , anti‐atherogenic , anti‐cancer , anti‐cardiovascular , anti‐diabetic , anti‐lipidemic , anti‐hypertensive , anti‐inflammatory , anti‐obesity , neuroprotective , and modulation of telomerase activities . In this review, we introduce the relationship between vitamin E and redox interactions with (i) absorption, distribution, metabolism, and excretion (ADME) of vitamin E, (ii) oxidative stress and reactive oxygen species (ROS) in the body, (iii) mechanism of antioxidative effects, (iv) non‐antioxidant functions of vitamin E, and (v) recent recognition of the field of oxidative stress research.…”

The Saccharomyces cerevisiae Hrq1 and Pif1 DNA helicases synergistically modulate telomerase activity in vitro

“…For instance, the transcription of human TERT can be altered genetically and epigenetically in cancers, leading to up-regulation of telomerase activity (5). Similarly, the transcription of genes encoding telomerase components and telomerase activity itself can be up-or down-regulated by various dietary compounds (6). Post-translational modifications of TERT, such as phosphorylation (7) and ubiquitination (8), also affect telomerase activity.…”