Xanthorrhizol inhibits non-small cell carcinoma (A549) cell growth and promotes apoptosis through modulation of PI3K/AKT and NF-κB signaling pathway
| Autor: | Zhaoying Sheng, Yong Cai, Jiying Wang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
DNA damage
Health Toxicology and Mutagenesis Apoptosis Management Monitoring Policy and Law Toxicology medicine.disease_cause Phosphatidylinositol 3-Kinases Phenols Cell Line Tumor medicine Humans Protein kinase B PI3K/AKT/mTOR pathway chemistry.chemical_classification A549 cell Reactive oxygen species TUNEL assay NF-kappa B General Medicine Cell biology chemistry A549 Cells Reactive Oxygen Species Proto-Oncogene Proteins c-akt Oxidative stress Signal Transduction |
| Zdroj: | Environmental toxicologyREFERENCES. 37(1) |
| ISSN: | 1522-7278 |
| Popis: | Xanthorrhizol (XNT) is a sesquiterpenoid agent isolated from Curcuma xanthorrhiza; It is known to exhibit various pharmacological activities including anti-cancer. We investigated the anti-cell proliferative and proapoptotic effects of XNT on Non-small cell carcinoma (A549) cells were analyzed by the generation of reactive oxygen species (ROS), alteration of mitochondrial membrane potential (ΔΨm), oxidative DNA damage, and apoptosis morphological changes were explored by Hoechst and AO/EtBr staining. Our study demonstrated that XNT treatment significantly reduced the viability of A549 cells in a concentration-dependent manner. We observed that XNT-induced oxidative stress-mediated apoptotic cell death by increasing intracellular ROS generation, depleting antioxidant levels, enhancing lipid peroxidation, increased apoptotic morphological changes, and % of DNA damage on human lung cancer cells. Furthermore, we observed that the XNT induce apoptosis through inhibits phosphorylation of PI3K, AKTand inhibit NF-κBp65 transcriptional signaling activity. In addition, XNT treatment alters the ΔΨm, thereby induces apoptosis was closely coordinated with the induction of pro-apoptotic markers Bax, Bad, caspase- 3, 9 and cytochrome c, and suppression of anti-apoptotic (Bcl-2, Bcl-XL) protein expression. According to our results, XNT-inducing apoptosis in A549 cells by causing oxidative damage and modulating apoptotic signaling events. Finally, XNT-induced apoptotic cell death was confirmed by the TUNEL assay. Therefore, XNT might be used as a chemotherapeutic agent for the treatment of lung cancer. |
| Databáze: | OpenAIRE |
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