Triptonide Modulates MAPK Signaling Pathways and Exerts Anticancer Effects via ER Stress-Mediated Apoptosis Induction in Human Osteosarcoma Cells.
ER stress
MAPK signaling
apoptosis
osteosarcoma
triptonide
Journal
Cancer management and research
ISSN: 1179-1322
Titre abrégé: Cancer Manag Res
Pays: New Zealand
ID NLM: 101512700
Informations de publication
Date de publication:
2020
2020
Historique:
received:
20
04
2020
accepted:
10
06
2020
entrez:
9
8
2020
pubmed:
9
8
2020
medline:
9
8
2020
Statut:
epublish
Résumé
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 In this study, we investigate the growth inhibitory effect of TN against human OS cells and its underlying molecular mechanism of action. 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. 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.
Sections du résumé
BACKGROUND
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
METHODS
METHODS
In this study, we investigate the growth inhibitory effect of TN against human OS cells and its underlying molecular mechanism of action.
RESULTS
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
CONCLUSIONS
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.
Identifiants
pubmed: 32765093
doi: 10.2147/CMAR.S258203
pii: 258203
pmc: PMC7373419
doi:
Types de publication
Journal Article
Langues
eng
Pagination
5919-5929Informations de copyright
© 2020 Zheng et al.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest in this work.
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