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

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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.

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Acknowledgments

This work has been supported by Ministry of Education (MOE) of Pakistan and China Scholarship Council (CSC) of China for a Doctoral Fellowship. The authors would like to acknowledge Wang Xiu-Li and Zhong Li Li for technical assistance during flow cytometry experiments and Syed Manzar Abbas Shah for critical reading of the manuscript.

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Authors and Affiliations

  1. Central Research Laboratory, Jilin University Bethune Second Hospital, Changchun, 130041, People’s Republic of China

    Azhar Rasul, Muhammad Khan, Yang Jing Bo & Tonghui Ma

  2. School of Life Sciences, Liaoning Normal University, Dalian, 116029, People’s Republic of China

    Bo Yu, Hong Yang & Tonghui Ma

  3. Institute of Biotechnology, Bahauddin Zakariya University, Multan, 60800, Pakistan

    Muhammad Ali

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  1. Azhar Rasul
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Correspondence to Tonghui Ma.

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Rasul, A., Khan, M., Yu, B. et al. Isoalantolactone, a sesquiterpene lactone, induces apoptosis in SGC-7901 cells via mitochondrial and phosphatidylinositol 3-kinase/Akt signaling pathways. Arch. Pharm. Res. 36, 1262–1269 (2013). https://doi.org/10.1007/s12272-013-0217-0

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