Sinensetin induces apoptosis and autophagy in the treatment of human T-cell lymphoma
| Autor: | Meng-Xian Lin, Kok-Tong Tan, Sheng-Hao Lin, Chi-Chien Lin, Shih-Chao Lin, Yu Tang Tung |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Cancer Research Programmed cell death MAP Kinase Kinase 4 Mice Nude Antineoplastic Agents Apoptosis Lymphoma T-Cell Jurkat cells 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Autophagy Tumor Cells Cultured Animals Humans Pharmacology (medical) Sinensetin Protein kinase B Cell Proliferation Pharmacology chemistry.chemical_classification Flavonoids Reactive oxygen species Mice Inbred BALB C Chemistry TOR Serine-Threonine Kinases Xenograft Model Antitumor Assays 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research Signal transduction Reactive Oxygen Species Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Anti-cancer drugs. 30(5) |
| ISSN: | 1473-5741 |
| Popis: | The present study was carried out to explore the effect of sinensetin in human T-cell lymphoma Jurkat cells and to reveal the underlying molecular mechanisms. We found that sinensetin significantly impeded Jurkat cell proliferation in a dose-dependent and time-dependent manner. Additionally, sinensetin treatment triggered apoptosis and autophagy in Jurkat cells. The apoptosis induction was related to a loss of mitochondrial membrane potential and to increased caspase-3/-8/-9 and poly(ADP-ribose) polymerase (PARP) cleavage. Sinensetin also induced autophagy, as evidenced by the formation of acidic vacuoles, the upregulation of LC3-II and beclin-1, and the downregulation of p62. In addition, the inhibition of autophagy by 3-methyladenine significantly enhanced the apoptosis rate and improved the sensitivity of the Jurkat cells to sinensetin. Moreover, sinensetin induced cell death, apoptosis, and autophagy through the activation of the reactive oxygen species/ c-Jun N-terminal kinase signaling pathway and the inhibition of the Akt/mTOR signaling pathways. In summary, our results revealed that sinensetin induced apoptosis and autophagy in human T-cell lymphoma Jurkat cells by activating reactive oxygen species/ c-Jun N-terminal kinase and blocking the Akt/mTOR signaling pathways. Thus, sinensetin might be a potential candidate in the development of antitumor drugs targeting T-cell leukemia. |
| Databáze: | OpenAIRE |
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