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http://ir.meiho.edu.tw/ir/handle/987654321/3885
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| 題名: | Involvement of Mitochondrial Dysfunction, Endoplasmic Reticulum Stress, and the PI3KAKTmTOR Pathway in Nobiletin-Induced Apoptosis of Human Bladder Cancer Cells |
| 作者: | Goan, Yih-Gang
Wu, Wen-Tung
Liu, Chih-I
Neoh, Choo-Aun
Wu, Yu-Jen |
| 貢獻者: | 健康暨護理學院 |
| 關鍵詞: | nobiletin
mitochondrial dysfunction
endoplasmic reticulum stress
PI3K/AKT/ mTOR pathway |
| 日期: | 2019 |
| 上傳時間: | 2020-09-24T05:51:18Z (UTC)
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| 摘要: | Nobiletin (NOB) is a polymethoxylated flavonoid isolated from citrus fruit peel that has been
shown to possess anti-tumor, antithrombotic, antifungal, anti-inflammatory and anti-atherosclerotic
activities. The main purpose of this study was to explore the potential of using NOB to induce
apoptosis in human bladder cancer cells and study the underlying mechanism. Using an MTT
assay, agarose gel electrophoresis, a wound-healing assay, flow cytometry, and western blot analysis,
this study investigated the signaling pathways involved in NOB-induced apoptosis in BFTC human
bladder cancer cells. Our results showed that NOB at concentrations of 60, 80, and 100 M inhibited
cell growth by 42%, 62%, and 80%, respectively. Cells treated with 60 M NOB demonstrated
increased DNA fragmentation, and flow cytometry analysis confirmed that the treatment caused
late apoptotic cell death. Western blot analysis showed that mitochondrial dysfunction occurred in
NOB-treated BFTC cells, leading to cytochrome C release into cytosol, activation of pro-apoptotic
proteins (caspase-3, caspase-9, Bad, and Bax), and inhibition of anti-apoptotic proteins (Mcl-1, Bcl-xl,
and Bcl-2). NOB-induced apoptosis was also mediated by regulating endoplasmic reticulum stress
via the PERK/elF2 /ATF4/CHOP pathway, and downregulating the PI3K/AKT/mTOR pathway.
Our results suggested that the cytotoxic and apoptotic e ects of NOB on bladder cancer cells are
associated with endoplasmic reticulum stress and mitochondrial dysfunction. |
| 顯示於類別: | [食品營養系] 期刊論文
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