TY  - JOUR
AU  - PARK Jae-woo
AU  - CHOI Woo-gyun
AU  - LEE Phil-jun
AU  - CHUNG Su-wol
AU  - KIM Byung-sam
AU  - CHUNG Hun-taeg
AU  - CHO Sungchan
AU  - KIM Jong-heon
AU  - KANG Byoung-heon
AU  - KIM Hyoungsu
AU  - KIM Hong-pyo
AU  - BACK Sung-hoon
PY  - 2017
TI  - The novel resveratrol derivative 3,5-diethoxy-3′,4′- dihydroxy- trans -stilbene induces mitochondrial ROS-mediated ER stress and cell death in human hepatoma cells  in vitro 
JF  - Acta Pharmacologica Sinica; Vol 38, No 11 (November 2017): Acta Pharmacologica Sinica
Y2  - 2017
KW  - 
N2  - Resveratrol (3,5,4′-trihydroxy- trans -stilbene) is a well-known polyphenol that is present in grapes, peanuts, pine seeds, and several other plants. Resveratrol exerts deleterious effects on various types of human cancer cells. Here, we analyzed the cell death-inducing mechanisms of resveratrol-006 (Res-006), a novel resveratrol derivative in human liver cancer cells  in vitro . Res-006 suppressed the viability of HepG2 human hepatoma cells more effectively than resveratrol (the IC 50  values were 67.2 and 354.8 μmol/L, respectively). Co-treatment with the ER stress regulator 4-phenylbutyrate (0.5 mmol/L) or the ROS inhibitor  N -acetyl- L -cysteine (NAC, 1 mmol/L) significantly attenuated Res-006-induced HepG2 cell death, suggesting that pro-apoptotic ER stress and/or ROS may govern the Res- 006-induced HepG2 cell death. We further revealed that treatment of HepG2 cells with Res-006 (65 μmol/L) immediately elicited the dysregulation of mitochondrial dynamics and the accumulation of mitochondrial ROS. It also collapsed the mitochondrial membrane potential and further induced ER stress and cell death. These events, except for the change in mitochondrial morphology, were prevented by the exposure of the HepG2 cells to the mitochondrial ROS scavenger, Mito-TEMPO (300–1000 μmol/L). The results suggest that Res-006 may kill HepG2 cells through cell death pathways, including the ER stress initiated by mitochondrial ROS accumulation. The cell death induced by this novel resveratrol derivative involves crosstalk between the mitochondria and ER stress mechanisms.
UR  - http://www.chinaphar.com/article/view/9678