Epigallocatechin-3-Gallate Induces Apoptosis as a TRAIL Sensitizer via Activation of Caspase 8 and Death Receptor 5 in Human Colon Cancer Cells

Abstract

Though epigallocatechin-3-gallate (EGCG), a major compound of green tea, has anti-diabetes, anti-obesity, anti-inflammatory, and antitumor effects, the underlying antitumor molecular mechanism of EGCG was not fully understood so far. Here the sensitizing effect of EGCG to tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) was examined in colorectal cancers. Cotreatment of EGCG and TRAIL synergistically enhanced cytotoxicity and sub G1 accumulation, increased the number of terminal deoxynucleotidyl transferase-dT-mediated dUTP nick end labelling (TUNEL)-positive cells in SW480 and HCT116 cells. Furthermore, this cotreatment promoted the cleavages of poly (adenosine diphosphate-ribose) polymerase (PARP) and induced caspase 8 activation compared to TRAIL or EGCG alone in SW480 and HCT116 cells. Of note, cotreatment of EGCG and TRAIL increased the expression of death receptor 5 (DR5) at protein and mRNA levels and also DR5 cell surface level in colon cancer cells. Conversely, depletion of DR5 reduced the apoptotic activity of cotreatment of EGCG and TRAIL to increase cytotoxicity, sub-G1 population and PARP cleavages in colon cancer cells. Overall, our findings provide evidence that EGCG can be a sensitizer of TRAIL via DR5 and caspase 8 mediated apoptosis in colorectal cancer cells.

The Potential of Epigallocatechin Gallate (EGCG) in Targeting Autophagy for Cancer Treatment: A Narrative Review

“…Accordingly, many cancer cells present low levels of death receptors which may trigger apoptosis by interacting with the TNF-related apoptosis-inducing ligand (TRAIL). Co-treatment with EGCG and TRAIL, of highly aggressive colon cancer cells, synergistically increased cytotoxicity, by upregulation of death receptors DR5 and activation of caspase 8 [ 44 ], demonstrating that EGCG can be a potent TRAIL sensitizer.…”

Epigallocatechin gallate triggers apoptosis by suppressing de novo lipogenesis in colorectal carcinoma cells

“…EGCG is the most abundant polyphenolic compound in dried green tea leaf extracts. Previous studies have reported that EGCG inhibits cell proliferation, metastasis and invasion, and also promotes apoptosis in various cancer cell types [27,29,45,46]. Another study revealed the anti‐metastatic effect of EGCG in the liver metastasis of human CRC [47].…”

Application of Polyphenols and Flavonoids in Oncological Therapy

“…In another example, the synergistic effect of EGCG and TRAIL (tumor necrosis factor (TNF)-induced apoptosis-inducing ligand), a cell death protein, enhances the activity of both caspase 8 and death receptor 5, resulting in the death of colon-cancer cells SW480 and HCT116 [ 95 ].…”