Gaillardin, a potent sesquiterpene lactone induces apoptosis via down-regulation of NF‐κβ in gastric cancer cells, AGS and MKN45

• Published in: Journal of ethnopharmacology 2021-12, Vol.281, p.114529-114529, Article 114529
• Main Authors: Roozbehani, Maryam, Abdolmohammadi, Mohammad Hossein, Hamzeloo-Moghadam, Maryam, Irani, Shiva, Fallahian, Faranak
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Cell Line, Tumor; Cell Survival - drug effects; Down-Regulation - drug effects; Gaillardin; Gastric cancer; Gene Expression Regulation - drug effects; Humans; Inflammation; Inula - chemistry; Lactones - chemistry; Lactones - pharmacology; Molecular Structure; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB; Plant Components, Aerial - chemistry; Sesquiterpene lactone; Sesquiterpenes - chemistry; Sesquiterpenes - pharmacology
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2021.114529

The genus Inula has been traditionally used as folk medicine in treating different illnesses such as kidney stones, urethra infection, jaundice, bronchitis, respiratory diseases and cancer. Gaillardin, a sesquiterpene lactone isolated from Inula oculus-christi, seems to have great potential as an anti-cancer agent. This study was carried out to evaluate the anti-cancer properties of Gaillardin in gastric cancer cells and also its possible underlying mechanism. The colorimetric MTT assay was used to assess metabolic activity of cells as an indicator of viability and cytotoxicity. Flow cytometry using Annexin V-FITC/PI was applied to detect and quantify the level of apoptosis. Detection of activated caspase-3, as a biochemical marker of apoptosis, was done using caspase-3 assay kit. Activation of NF-κB pathway was determined by western blotting. The mRNA expression levels of NF-κB target genes were measured using quantitative RT-PCR. Moreover, intracellular reactive oxygen species (ROS) production was evaluated. Gaillardin significantly reduced cell viability in a time and dose-dependent manner. The inhibitory effect of Gaillardin was attributed to induction of apoptosis. Investigation about the underlying mechanism revealed that Gaillardin exerts its action through inhibition of NF-κB activation and subsequently down-regulation of genes (COX-2, MMP-9, TWIST-1, and BCl-2) regulated by NF-κB. Moreover, Gaillardin caused remarkable elevation in ROS production in AGS and MKN45 cells. We provided evidences about the role of NF-κB pathway in the induction of apoptosis by the sesquiterpene lactone Gaillardin in AGS and MKN45 cells for the first time, which suggest Gaillardin could be considered as a promising natural agent for further investigations to identify new potent anticancer drugs in the future. [Display omitted] •Gaillardin induced cell growth inhibition in AGS and MKN45 cells.•Apoptotic cell death was involved in Gaillardin-mediated cytotoxicity.•Apoptotic effects of Gaillardin might be attributed to inhibition of NF-κB pathway.•Down-regulation of COX-2, MMP-9, TWIST-1, BCl-2, and up-regulation of Bax were detected in treated cells with Gaillardin.•ROS level was remarkably increased in response to Gaillardin.