PMID- 32283836 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 2227-9059 (Print) IS - 2227-9059 (Electronic) IS - 2227-9059 (Linking) VI - 8 IP - 4 DP - 2020 Apr 9 TI - Epigallocatechin-3-Gallate Induces Apoptosis as a TRAIL Sensitizer via Activation of Caspase 8 and Death Receptor 5 in Human Colon Cancer Cells. LID - 10.3390/biomedicines8040084 [doi] LID - 84 AB - 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. FAU - Kwon, Oh Sung AU - Kwon OS AD - College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. FAU - Jung, Ji Hoon AU - Jung JH AD - College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. FAU - Shin, Eun Ah AU - Shin EA AD - College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. FAU - Park, Ji Eon AU - Park JE AD - College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. FAU - Park, Woon Yi AU - Park WY AD - College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. FAU - Kim, Sung-Hoon AU - Kim SH AD - College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. LA - eng GR - 2017R1A2A1A17069297/National Research Foundation of Korea/ PT - Journal Article DEP - 20200409 PL - Switzerland TA - Biomedicines JT - Biomedicines JID - 101691304 PMC - PMC7235876 OTO - NOTNLM OT - DR5 OT - EGCG OT - TRAIL OT - apoptosis OT - caspase OT - colon cancer COIS- The authors declare no conflict of interest. EDAT- 2020/04/15 06:00 MHDA- 2020/04/15 06:01 PMCR- 2020/04/09 CRDT- 2020/04/15 06:00 PHST- 2020/03/25 00:00 [received] PHST- 2020/04/07 00:00 [revised] PHST- 2020/04/08 00:00 [accepted] PHST- 2020/04/15 06:00 [entrez] PHST- 2020/04/15 06:00 [pubmed] PHST- 2020/04/15 06:01 [medline] PHST- 2020/04/09 00:00 [pmc-release] AID - biomedicines8040084 [pii] AID - biomedicines-08-00084 [pii] AID - 10.3390/biomedicines8040084 [doi] PST - epublish SO - Biomedicines. 2020 Apr 9;8(4):84. doi: 10.3390/biomedicines8040084.