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

College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomedicines 2020, 8(4), 84; https://doi.org/10.3390/biomedicines8040084
Received: 25 March 2020 / Revised: 7 April 2020 / Accepted: 8 April 2020 / Published: 9 April 2020
(This article belongs to the Section Cancer Therapeutics)
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. View Full-Text
Keywords: EGCG; TRAIL; colon cancer; caspase; DR5; apoptosis EGCG; TRAIL; colon cancer; caspase; DR5; apoptosis
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Kwon, O.S.; Jung, J.H.; Shin, E.A.; Park, J.E.; Park, W.Y.; Kim, S.-H. Epigallocatechin-3-Gallate Induces Apoptosis as a TRAIL Sensitizer via Activation of Caspase 8 and Death Receptor 5 in Human Colon Cancer Cells. Biomedicines 2020, 8, 84.

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