3,4,5-Tricaffeoylquinic Acid Attenuates TRAIL-induced Apoptosis in Human Keratinocytes by Suppressing Apoptosis-related Protein Activation.

Abstract

Caffeoyl derivatives exhibit antiinflammatory and antioxidant effects. However, the effect of 3,4,5-tricaffeoylquinic acid on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in keratinocytes that may be involved in skin diseases has not been studied. In this respect, we investigated the effect of 3,4,5-tricaffeoylquinic acid on TRAIL-induced apoptosis in human keratinocytes. 3,4,5-Tricaffeoylquinic acid and oxidant scavengers attenuated the decrease in the cytosolic levels of Bid, Bcl-2, and survivin proteins; the increase in the levels of cytosolic Bax, p53, and phosphorylated p53; the increase in the levels of phosphorylated p38; the increase in the mitochondrial levels of the voltage-dependent anion channel; loss of the mitochondrial transmembrane potential; the release of cytochrome c; activation of caspases (8, 9, and 3); cleavage of poly [ADP-ribose] polymerase-1; production of reactive oxygen species; the depletion of glutathione (GSH); nuclear damage; and cell death in keratinocytes treated with TRAIL. These results suggest that 3,4,5-tricaffeoylquinic acid may reduce TRAIL-induced apoptosis in human keratinocytes by suppressing the activation of the caspase-8 and Bid pathways and the mitochondria-mediated cell death pathway. The effect appears to be associated with the inhibitory effect on the production of reactive oxygen species and depletion of GSH. 3,4,5-Tricaffeoylquinic acid appears to be effective in the prevention of TRAIL-induced apoptosis-mediated skin diseases.

• Authors: Da Hee Lee, Yoon Jeong Nam, Min Sung Lee, Dong Suep Sohn, Yong Kyoo Shin, Chung Soo Lee
• Journal: Phytotherapy research : PTR (Phytother Res) Vol. 29 Issue 10 Pg. 1549-58 (Oct 2015) ISSN: 1099-1573 [Electronic] England
• PMID: 26224159 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 John Wiley & Sons, Ltd.

Chemical References

• Reactive Oxygen Species
• TNF-Related Apoptosis-Inducing Ligand
• caffeoylquinic acid
• Quinic Acid
• Cytochromes c
• Caspase 8
• Caspases
• Glutathione

Topics

• Apoptosis (drug effects)
• Caspase 8 (metabolism)
• Caspases (metabolism)
• Cell Death
• Cytochromes c (metabolism)
• Cytosol (metabolism)
• Glutathione (metabolism)
• Humans
• Keratinocytes (drug effects, pathology)
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects)
• Quinic Acid (analogs & derivatives, chemistry)
• Reactive Oxygen Species (metabolism)
• TNF-Related Apoptosis-Inducing Ligand (pharmacology)