Sedanolide induces autophagy through the PI3K, p53 and NF-κB signaling pathways in human liver cancer cells.

Abstract

Sedanolide (SN), a phthalide-like compound from celery seed oil, possesses antioxidant effects. However, the effect of SN on cell death in human liver cancer cells has yet to be determined. In this study, cell viability determination, monodansylcadaverine (MDC) fluorescent staining and immunoblot analysis were performed to determine autophagy induction and autophagy-induced protein expression changes via molecular examination after human liver cancer (J5) cells were treated with SN. Our studies demonstrate that SN suppressed J5 cell viability by inducing autophagy. Phosphoinositide 3-kinase (PI3K)-I, mammalian target of rapamycin (mTOR) and Akt protein levels decreased, whereas PI3K-III, LC3-II and Beclin-1 protein levels increased following SN treatment in J5 cells. In addition, SN treatment upregulated nuclear p53 and damage-regulated autophagy modulator (DRAM) and downregulated cytosolic p53 and Tp53-induced glycolysis and apoptosis regulator (TIGAR) expression in J5 cells. Furthermore, the cytosolic phosphorylation of inhibitor of kappa B (IκB) and nuclear p65 and the DNA-binding activity of NF-κB increased after SN treatment. These results suggest that SN induces J5 cell autophagy by regulating PI3K, p53 and NF-κB autophagy-associated signaling pathways in J5 cells.

• Authors: Shu-Ling Hsieh, Chi-Tsai Chen, Jyh-Jye Wang, Yu-Hao Kuo, Chien-Chun Li, Lan-Chi Hsieh, Chih-Chung Wu
• Journal: International journal of oncology (Int J Oncol) Vol. 47 Issue 6 Pg. 2240-6 (Dec 2015) ISSN: 1791-2423 [Electronic] Greece
• PMID: 26500073 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Benzofurans
• NF-kappa B
• TP53 protein, human
• Tumor Suppressor Protein p53
• neocnidilide
• Phosphatidylinositol 3-Kinases

Topics

• Antineoplastic Agents (pharmacology)
• Autophagy (drug effects, physiology)
• Benzofurans (pharmacology)
• Carcinoma, Hepatocellular (metabolism, pathology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Humans
• Immunoblotting
• Liver Neoplasms (metabolism, pathology)
• NF-kappa B (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Signal Transduction (drug effects)
• Tumor Suppressor Protein p53 (metabolism)