Targeting PPARγ/ NF-κB Signaling Pathway by Britannin, a Sesquiterpene Lactone from Inula aucheriana DC., in Gastric Cancer


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Background: Gastric cancer is one of the most common and deadliest malignancies in the world. Therefore, there is an urgent need to develop new and effective agents to reduce mortality. The plants of genus Inula have gained the attention of researchers worldwide as a rich source of potent medicinal compounds.

Objective: This study explores the anti-cancer activity of Britannin, a sesquiterpene lactone isolated from Inula aucheriana DC., and its molecular mechanism in gastric cancer cells, AGS and MKN45

Methods: Cytotoxicity was evaluated through the MTT assay following 24 h, 48 h, and 72 h treatment with different concentrations of Britannin. Apoptosis rate and caspase-3 activity were measured 24 h after treatment by Britannin. . Western blotting was performed to determine the expression of the NF-κB, IκBα, and PPARγ proteins. Moreover, quantitative RT-PCR was applied to measure the expression of NF-κB target genes.

Results: We showed that Britannin induced cell growth inhibition and apoptosis in gastric cancer cells. Britannin caused an elevation in mRNA and protein levels of PPARγ. The involvement of PPARγ was more confirmed using GW9662, a PPARγ inhibitor. Suppression of NF-κB was demonstrated by western blot analysis. Down-regulation of MMP-9, TWIST-1, COX-2, and Bcl-2 and up-regulation of Bax were also observed in gastric cancer cells.

Conclusion: These results imply that activation of the PPARγ signaling pathway through suppression of NF-κB underlies the anti-cancer properties of Britannin in gastric cancer. Therefore, Britannin could be considered as a promising anti-cancer candidate for further evaluation.

Sobre autores

Mohammad Abdolmohammadi

Cellular and Molecular Research Center, Qom University of Medical Sciences

Email: info@benthamscience.net

Maryam Roozbehani

Department of Biology, Science and Research Branch, Islamic Azad University

Email: info@benthamscience.net

Maryam Hamzeloo-Moghadam

Traditional Medicine and Materia Medica Research Center, Beheshti University of Medical Sciences and Department of Traditional Pharmacy, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences

Email: info@benthamscience.net

Fatemeh Heidari

Cellular and Molecular Research Center, Qom University of Medical Sciences

Email: info@benthamscience.net

Faranak Fallahian

Cellular and Molecular Research Center, Qom University of Medical Sciences

Autor responsável pela correspondência
Email: info@benthamscience.net

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