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Triptolide induces apoptosis through the calcium/calmodulin‑dependent protein kinase kinaseβ/AMP‑activated protein kinase signaling pathway in non‑small cell lung cancer cells.
- Source :
-
Oncology reports [Oncol Rep] 2020 Nov; Vol. 44 (5), pp. 2288-2296. Date of Electronic Publication: 2020 Sep 11. - Publication Year :
- 2020
-
Abstract
- Triptolide, a triterpene extracted from the Chinese herb Tripterygium wilfordii, has been reported to exert multiple bioactivities, including immunosuppressive, anti‑inflammatory and anticancer effects. Although the anticancer effect of triptolide has attracted significant attention, the specific anticancer mechanism in non‑small‑cell lung cancer (NSCLC) remains unclear. The present study aimed to investigate the anticancer effect of triptolide in the H1395 NSCLC cell line and to determine its mechanism of action. The results revealed that triptolide significantly inhibited the cell viability of NSCLC cells in a dose‑dependent manner, which was suggested to be through inducing apoptosis. In addition, triptolide was revealed to activate the calcium (Ca2+)/calmodulin‑dependent protein kinase kinase β (CaMKKβ)/AMP‑activated protein kinase (AMPK) signaling pathway by regulating the intracellular Ca2+ concentration levels, which increased the phosphorylation levels of AMPK and reduced the phosphorylation levels of AKT, ultimately leading to apoptosis. The CaMKKβ blocker STO‑609 and the AMPK blocker Compound C significantly inhibited the apoptosis‑promoting effect of triptolide. In conclusion, the results of the present study suggested that triptolide may induce apoptosis through the CaMKKβ‑AMPK signaling pathway and may be a promising drug for the treatment of NSCLC.
- Subjects :
- AMP-Activated Protein Kinases antagonists & inhibitors
AMP-Activated Protein Kinases metabolism
Benzimidazoles pharmacology
Calcium analysis
Calcium metabolism
Calcium-Calmodulin-Dependent Protein Kinase Kinase antagonists & inhibitors
Calcium-Calmodulin-Dependent Protein Kinase Kinase metabolism
Carcinoma, Non-Small-Cell Lung pathology
Cell Line, Tumor
Diterpenes therapeutic use
Epoxy Compounds pharmacology
Epoxy Compounds therapeutic use
Humans
Lung Neoplasms pathology
Naphthalimides pharmacology
Phenanthrenes therapeutic use
Phosphorylation drug effects
Pyrazoles pharmacology
Pyrimidines pharmacology
Signal Transduction drug effects
Apoptosis drug effects
Carcinoma, Non-Small-Cell Lung drug therapy
Diterpenes pharmacology
Lung Neoplasms drug therapy
Phenanthrenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2431
- Volume :
- 44
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Oncology reports
- Publication Type :
- Academic Journal
- Accession number :
- 33000264
- Full Text :
- https://doi.org/10.3892/or.2020.7763