Isoalantolactone, a sesquiterpene lactone, induces apoptosis in SGC-7901 cells via mitochondrial and phosphatidylinositol 3-kinase/Akt signaling pathways.

Abstract

Isoalantolactone, a sesquiterpene lactone, possesses anti-fungal as well as cytotoxic properties. In this study, the effects of Isoalantolactone on cell viability, cell cycle, and apoptosis were investigated in human gastric adenocarcinoma SGC-7901 cells. The results demonstrated that Isoalantolactone induced morphological changes and decreased cell viability. Subsequently, we found that Isoalantolactone induced G2/M and S phase arrest, which was associated with a decrease in the expression level of cyclin B1. Apoptosis triggered by Isoalantolactone was visualized using propidium iodide (PI) and Annexin V-FITC/PI staining. Isoalantolactone-induced apoptosis of SGC-7901 cells was associated with the dissipation of mitochondrial membrane potential (ΔΨ m) that was due to the down-regulation of Bcl-2 and up-regulation of Bax that led to the cleavage of caspase-3. Additionally, it was found that Isoalantolactone was involved in the inhibition of phosphorylation of PI3K/Akt. Isoalantolactone-induced cytotoxicity and apoptosis of SGC-7901 cells involve mitochondria-caspase and PI3K/Akt dependent pathways, which gives the rationale for in vivo studies on the utilization of Isoalantolactone as a potential cancer therapeutic compound.

• Authors: Azhar Rasul, Muhammad Khan, Bo Yu, Muhammad Ali, Yang Jing Bo, Hong Yang, Tonghui Ma
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 36 Issue 10 Pg. 1262-9 (Oct 2013) ISSN: 1976-3786 [Electronic] Korea (South)
• PMID: 23881702 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclin B1
• Sesquiterpenes
• isoalantolactone
• Phosphatidylinositol 3-Kinase
• Proto-Oncogene Proteins c-akt
• Caspases

Topics

• Apoptosis (drug effects)
• Caspases (metabolism)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cyclin B1 (biosynthesis)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, enzymology, metabolism)
• Phosphatidylinositol 3-Kinase (metabolism)
• Phosphorylation (drug effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Sesquiterpenes (toxicity)
• Signal Transduction (drug effects)