|
KMID : 0613820140240090927
|
|
Journal of Life Science
2014 Volume.24 No. 9 p.927 ~ p.934
|
|
|
Sanguinarine Increases Sensitivity of Human Gastric Adenocarcinoma Cells to TRAIL-mediated Apoptosis by Inducing DR5 Expression and ROS Generation
|
|
Lee Taek-Ju
Im Yong-Gyun
Choi Woo-Young
Choi Sung-Hyun
Hwang Won-Deok
Choi Yung-Hyun
|
|
|
Abstract
|
|
|
|
Sanguinarine, a benzophenanthridine alkaloid originally derived from the root of Sanguinaria canadensis, has been shown to possess antimicrobial, antioxidant, and anti-cancer properties. Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to induce apoptosis in cancer cells, but not most normal cells and has shown efficacy in a phase 2 clinical trial, development of resistance to TRAIL by tumor cells is a major roadblock. Our previous study indicated that treatment with TRAIL in combination with subtoxic concentrations of sanguinarine sensitized TRAIL-mediated apoptosis in TRAIL-resistant human gastric carcinoma AGS cells; however, the detailed mechanisms are not fully understood. In this study, we show that sanguinarine sensitizes AGS cells to TRAIL- mediated apoptosis as detected by MTT assay, agarose gel electrophoresis, chromatin condensation and flow cytometry analysis. Combined treatment with sanguinarine and TRAIL effectively induced expression of death receptor (DR) 5 but did not affect expression of DR4 and mitogen activated protein kinases signaling molecules. Moreover, the combined treatment with sanguinarine and TRAIL increased the generation of reactive oxygen species (ROS); however, N-acetylcysteine, ROS scavenger, significantly recovered growth inhibition induced by the combined treatment. Taken together, our results indicate that sanguinarine can potentiate TRAIL-mediated apoptosis through up-regulation of DR5 expression and ROS generation.
|
|
|
KEYWORD
|
|
|
Apoptosis, death receptor 5, reactive oxygen species, sanguinarine, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|