Triptonide Modulates MAPK Signaling Pathways and Exerts Anticancer Effects via ER Stress-Mediated Apoptosis Induction in Human Osteosarcoma Cells.
Cancer Manag Res
; 12: 5919-5929, 2020.
Article
em En
| MEDLINE
| ID: mdl-32765093
ABSTRACT
BACKGROUND:
Osteosarcoma (OS) is the most common primary malignancy arise from bone and is one of the causes of cancer-related deaths. Triptonide (TN), a diterpenoid epoxide presented in Tripterygium wilfordii, is shown to possess a broad spectrum of biological properties.METHODS:
In this study, we investigate the growth inhibitory effect of TN against human OS cells and its underlying molecular mechanism of action.RESULTS:
Findings of our in vitro study revealed that TN exhibited a dose-dependent cytotoxic effect in MG63 and U-2OS cells. ROS-mediated cytotoxic effect was achieved in OS cells treated with TN which was reversed upon NAC treatment. Significantly, increased expression of PERK, p-EIF2, GRP78, ATF4 and CHOP in TN-treated OS cells unfolds the molecular mechanism of TN targets ER stress-mediated apoptosis. Modulation of ERK MAPK pathway was also observed as evidenced by the increased phosphorylation of ERK (p-ERK) and p-p38 in TN-treated OS cells.CONCLUSION:
Altogether, the outcome of the study for the first time revealed that TN exhibited its potential chemotherapeutic effects through ROS-mediated ER stress-induced apoptosis via p38 and ERK MAPK signaling pathways.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Cancer Manag Res
Ano de publicação:
2020
Tipo de documento:
Article