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Coronarin D induces apoptotic cell death through the JNK pathway in human hepatocellular carcinoma.
- Source :
-
Environmental toxicology [Environ Toxicol] 2018 Sep; Vol. 33 (9), pp. 946-954. Date of Electronic Publication: 2018 Jul 03. - Publication Year :
- 2018
-
Abstract
- Coronarin D, a diterpene derived from the rhizomes of Hedychium coronarium, has been used to treat inflammatory diseases. Coronarin D can exert strong anticancer effects through cell growth prevention and cell cycle arrest in many cancer cells. In this study, we investigated the molecular mechanism through which coronarin D suppresses cell proliferation and triggers cell death in human hepatocellular carcinoma (HCC) cells. Treatment of Huh7 and Sk-hep-1 cells with coronarin D resulted in a significantly increased loss of mitochondrial membrane potential, leading to the cleavage and activation of caspase-9, caspase-8, and caspase-3 and changes in Bax, Bcl-2, and Bcl-xL protein levels. Coronarin D significantly induced autophagy by increasing the expression of Beclin-1 and LC3-II and reducing the expression of p62. Moreover, Huh7 and Sk-hep-1 cells exposed to coronarin D had decreased expression of phosphorylated AKT, p38, and ERK and increased expression of phosphorylated JNK. Exposure of cells to the JNK-specific inhibitor SP600125 attenuated the apoptotic effects of coronarin D. Taken together, this is the first study to report that coronarin D may effectively inhibit cell growth through apoptosis. We have provided evidence indicating that coronarin D induces cell death through the upregulation of JNK mitogen-activated protein kinases in human HCC cells.<br /> (© 2018 Wiley Periodicals, Inc.)
- Subjects :
- Autophagy drug effects
Caspase 3 metabolism
Caspase 8 metabolism
Caspase 9 metabolism
Cell Line, Tumor
Cell Proliferation drug effects
Humans
MAP Kinase Signaling System
Phosphorylation
Up-Regulation
bcl-X Protein metabolism
Antineoplastic Agents, Phytogenic pharmacology
Apoptosis drug effects
Carcinoma, Hepatocellular pathology
Diterpenes pharmacology
JNK Mitogen-Activated Protein Kinases metabolism
Liver Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-7278
- Volume :
- 33
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Environmental toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 29968959
- Full Text :
- https://doi.org/10.1002/tox.22579