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Oridonin‐induced mitochondria‐dependent apoptosis in esophageal cancer cells by inhibiting PI3K/AKT/mTOR and Ras/Raf pathways
- Source :
- Journal of Cellular Biochemistry. 120:3736-3746
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
Abstract
- Oridonin, an active diterpenoid isolated from Rabdosia rubescens, has been reported for its antitumor activity on several cancers. However, its effect on human esophageal cancer remains unclear. In this study, we demonstrated that oridonin could inhibit the growth of human esophageal cancer cells both in vitro and in vivo. Oridonin not only suppressed the proliferation, but also induced cell cycle arrest and mitochondrial-mediated apoptosis in KYSE-30, KYSE-150, and EC9706 cells with dose-dependent manner. Further mechanism studies revealed that oridonin led cell cycle arrest in esophageal cancer cells via downregulating cell cycle-related proteins, such as cyclin B1 and CDK2, while upregulating p53 and p21. Oridonin also increased proapoptotic protein Bax and reduced antiapoptotic protein Bcl-2, as well as the increased expression of cleaved caspase-3, -8, and -9. In addition, oridonin treatment could significantly inhibit the PI3K/Akt/mTOR and Ras/Raf signaling pathway. In vivo results further demonstrated that oridonin treatment markedly inhibited tumor growth in the esophageal cancer xenograft mice model. Taken together, these results suggest that oridonin may be a potential anticancer agent for the treatment of esophageal cancer.
- Subjects :
- Cyclin-Dependent Kinase Inhibitor p21
0301 basic medicine
Cell cycle checkpoint
Esophageal Neoplasms
Cell
Mice, Nude
Apoptosis
Biochemistry
Mice
Phosphatidylinositol 3-Kinases
03 medical and health sciences
0302 clinical medicine
Cell Movement
Cell Line, Tumor
medicine
Animals
Humans
Cyclin B1
Molecular Biology
Protein kinase B
PI3K/AKT/mTOR pathway
Cell Proliferation
bcl-2-Associated X Protein
biology
Chemistry
TOR Serine-Threonine Kinases
Cyclin-Dependent Kinase 2
Cyclin-dependent kinase 2
Cell Biology
Antineoplastic Agents, Phytogenic
Xenograft Model Antitumor Assays
Mitochondria
Tumor Burden
Gene Expression Regulation, Neoplastic
030104 developmental biology
medicine.anatomical_structure
Proto-Oncogene Proteins c-bcl-2
030220 oncology & carcinogenesis
Cancer research
biology.protein
Female
Tumor Suppressor Protein p53
Signal transduction
Diterpenes, Kaurane
Proto-Oncogene Proteins c-akt
Signal Transduction
Subjects
Details
- ISSN :
- 10974644 and 07302312
- Volume :
- 120
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular Biochemistry
- Accession number :
- edsair.doi.dedup.....f3571e73db2a5887fe9f767d27f8d828