Sesamin suppresses NSCLC cell proliferation and induces apoptosis via Akt/p53 pathway
| Autor: | Zhicheng Yang, Bing Liu, Changpeng Lu, Luyong Zhang, Huachao Li, Wanchen Qi, Yueming Chen, Huiliang Huang, Weinan Zhang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cell cycle checkpoint Lung Neoplasms Morpholines Apoptosis Dioxoles Toxicology Lignans 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Cyclin D1 Sesamin Carcinoma Non-Small-Cell Lung Cell Line Tumor Animals Humans MTT assay Benzothiazoles Protein kinase B Cell Proliferation Pharmacology Cell growth Cell cycle G1 Phase Cell Cycle Checkpoints Xenograft Model Antitumor Assays 030104 developmental biology chemistry Chromones 030220 oncology & carcinogenesis Cancer research Female Tumor Suppressor Protein p53 Proto-Oncogene Proteins c-akt Signal Transduction Toluene |
| Zdroj: | Toxicology and applied pharmacology. 387 |
| ISSN: | 1096-0333 |
| Popis: | Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with a disappointing prognosis. The aim of this study was to investigate the anticancer effect of sesamin and the underlying mechanism. The MTT assay was used to detect the proliferation of NSCLC cells. The cell cycle and apoptosis were analyzed by flow cytometry. The protein levels of Akt, p-Akt (Ser473), p53, cyclin D1, CDK2, MDM2, p-MDM2 (Ser166) were detected by western blotting. The expression of p-Akt (Ser473), p53 and Ki67 in vivo was analyzed by IHC. Histopathologic analyses of major organs (heart, liver, spleen, lung and kidney) were performed by H&E staining. The results show that sesamin suppressed cell proliferation and induced apoptosis of NSCLC cells (A549 and H1792) in a dose-dependent manner. Treatment with sesamin caused cell cycle arrest at G1 phase and inhibited cyclin D1 and CDK2 expression. In addition, sesamin inhibited Akt activity and upregulated p53 expression both in vivo and in vitro. When Akt and p53 were suppressed by LY294002 and PFTα, respectively, sesamin exerted no additional effects. The in vivo results mostly matched the in vitro findings. Specifically, sesamin exerted little damage to major organs. Taken together, this study demonstrates that sesamin suppresses NSCLC cell proliferation by induction of G1 phase cell cycle arrest and apoptosis via Akt/p53 pathway. Therefore, sesamin may be a promising adjuvant treatment for NSCLC therapy. |
| Databáze: | OpenAIRE |
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