4.6 Article

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

Journal

ARCHIVES OF PHARMACAL RESEARCH
Volume 36, Issue 10, Pages 1262-1269

Publisher

PHARMACEUTICAL SOC KOREA
DOI: 10.1007/s12272-013-0217-0

Keywords

Isoalantolactone; Sesquiterpene lactone; SGC-7901 cells; Apoptosis; PI3K/Akt pathway

Funding

  1. Ministry of Education (MOE) of Pakistan
  2. China Scholarship Council (CSC) of China

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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 (Delta I (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.

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