phyllanthin and epigallocatechin-gallate

Direct scavenging of reactive oxygen species could not prevent ER stress-associated cytotoxicity of indomethacin or diclofenac in Caco-2 cells. This study investigated the effects of three polyphenolic antioxidants epigallocatechin gallate (EGCG), phyllanthin and hypophyllathin in non-steroidal anti-inflammatory drug-induced Caco-2 apoptosis.. Cells were treated with ER stressors (indomethacin, diclofenac, tunicamycin or thapsigargin) and the polyphenols for up to 72 h. Cell viability, apoptosis and mitochondrial function were monitored by MTT, Hoechst 33342 and TMRE assays, respectively. Protein expression was measured by Western blot analysis.. Epigallocatechin gallate suppressed increases in p-PERK/p-eIF-2α/ATF-4/CHOP and p-IRE-1α/p-JNK1/2 expression levels in the cells treated with any of the ER stressors, leading to inhibition of apoptosis. In contrast, phyllanthin increased apoptosis in the cells subsequently exposed to either diclofenac, tunicamycin or thapsigargin, but not in the indomethacin-treated cells. The potentiation effect of phyllanthin seen with the three ER stressors was related to suppression of survival p-Nrf-2/HO-1 expression, resulting in increased activation of the eIF-2α/ATF-4/CHOP pathway. On the other hand, hypophyllanthin had no significant effect on the ER stressor-induced apoptosis.. Epigallocatechin gallate, phyllanthin and hypophyllanthin displayed different effects in the ER stress-mediated apoptosis, depending upon their interaction with the specific unfolded protein response signalling.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Apoptosis; Caco-2 Cells; Catechin; Diclofenac; Endoplasmic Reticulum Stress; Humans; Indomethacin; Intestinal Mucosa; Lignans; Mitochondria; Oxidative Stress; Signal Transduction; Thapsigargin; Tunicamycin; Unfolded Protein Response