Abstract
Epigallocatechin-3-gallate (EGCG) is the most abundant bioactive polyphenolic compound among the green tea constituents and has been identified as a potential anticancer agent in colorectal cancer (CRC) studies. This study was aimed to determine the mechanism of actions of EGCG when targeting the endoplasmic reticulum (ER) stress pathway in CRC. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay was performed on HT-29 cell line and normal cell line (3T3) to determine the EGCG toxicity. Next, western blot was done to observe the expression of the related proteins for the ER stress pathway. The Caspase 3/7 assay was performed to determine the apoptosis induced by EGCG. The results demonstrated that EGCG treatment was toxic to the HT-29 cell line. EGCG induced ER stress in HT-29 by upregulating immunoglobulin-binding (BiP), PKR-like endoplasmic reticulum kinase (PERK), phosphorylation of eukaryotic initiation factor 2 alpha subunit (eIF2α), activating transcription 4 (ATF4), and inositol-requiring kinase 1 alpha (IRE1α). Apoptosis was induced in HT-29 cells after the EGCG treatment, as shown by the Caspase 3/7 activity. This study indicates that green tea EGCG has the potential to inhibit colorectal cancer cells through the induction of ER stress.
Highlights
Green tea has long been a part of human life, and its earliest consumption can be dated back from 500,000 years ago
A similar observation was seen following 48 and 72 h of treatment. e viability of the cells was affected by the duration of EGCG exposure. us, the toxicity of EGCG depends on the dose and duration of exposure. is clearly showed the toxicity of the EGCG towards the colorectal cancer cells in a dose-dependent manner
Since the study has demonstrated the toxicity of EGCG at inhibiting the growth of colorectal cancer cell lines, its toxicity has been tested on the normal cell line, 3T3 (Figure 3). is embryonic fibroblast cell line (3T3) has shown that the EGCG was not toxic to normal healthy cells, given the treatment at any concentration even at the highest concentration of EGCG (1000 μM)
Summary
Green tea has long been a part of human life, and its earliest consumption can be dated back from 500,000 years ago. It has been observed to suppress breast cancer [5,6,7], prostate cancer [8,9,10], lung cancer [11,12,13], pancreatic cancer [14,15,16], and liver cancer [17, 18]. All of this anticancer activity by EGCG has previously been demonstrated that EGCG is the most effective cancer chemopreventive polyphenol in green tea [19]. Rady et al reviewed that all of these anticancer effects by EGCG work by apoptosis induction, control in cell proliferation, and/or inhibition of angiogenesis [20]. ese mechanisms have previously been suggested by Min and Kwon, and they added inhibition in metastasis; tumorigenesis is an important mechanism adapted by EGCG to unveil their anticancer properties [21]
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