https://scholars.lib.ntu.edu.tw/handle/123456789/466426
標題: | Sulindac compounds facilitate the cytotoxicity of β-lapachone by up-regulation of NAD(P)H quinone oxidoreductase in human lung cancer cells | 作者: | HSIU-NI KUNG Weng T.-Y. Liu Y.-L. KUO-SHYAN LU Chau Y.-P. |
公開日期: | 2014 | 出版社: | Public Library of Science | 卷: | 9 | 期: | 2 | 起(迄)頁: | e88122 | 來源出版物: | PLoS ONE | 摘要: | β-lapachone, a major component in an ethanol extract of Tabebuia avellanedae bark, is a promising potential therapeutic drug for various tumors, including lung cancer, the leading cause of cancer-related deaths worldwide. In the first part of this study, we found that apoptotic cell death induced in lung cancer cells by high concentrations of β-lapachone was mediated by increased activation of the pro-apoptotic factor JNK and decreased activation of the cell survival/proliferation factors PI3K, AKT, and ERK. In addition, β-lapachone toxicity was positively correlated with the expression and activity of NAD(P)H quinone oxidoreductase 1 (NQO1) in the tumor cells. In the second part, we found that the FDA-approved non-steroidal anti-inflammatory drug sulindac and its metabolites, sulindac sulfide and sulindac sulfone, increased NQO1 expression and activity in the lung adenocarcinoma cell lines CL1-1 and CL1-5, which have lower NQO1 levels and lower sensitivity to β-lapachone treatment than the A549 cell lines, and that inhibition of NQO1 by either dicoumarol treatment or NQO1 siRNA knockdown inhibited this sulindac-induced increase in β-lapachone cytotoxicity. In conclusion, sulindac and its metabolites synergistically increase the anticancer effects of β-lapachone primarily by increasing NQO1 activity and expression, and these two drugs may provide a novel combination therapy for lung cancers. ? 2014 Kung et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84895515192&doi=10.1371%2fjournal.pone.0088122&partnerID=40&md5=18d0e1b420f29e95329dce9fd04fe8a9 https://scholars.lib.ntu.edu.tw/handle/123456789/466426 |
ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0088122 | SDG/關鍵字: | beta lapachone; mitogen activated protein kinase; phosphatidylinositol 3 kinase; protein kinase B; reduced nicotinamide adenine dinucleotide (phosphate) dehydrogenase (quinone); stress activated protein kinase; sulindac; sulindac sulfide; sulindac sulfone; antineoplastic activity; apoptosis; article; cancer cell culture; cancer resistance; cell proliferation; cell survival; concentration response; controlled study; down regulation; drug cytotoxicity; drug potentiation; drug sensitivity; drug targeting; enzyme activation; enzyme regulation; human; human cell; lung adenocarcinoma; lung cancer; protein expression; signal transduction; upregulation; Adenocarcinoma; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Cell Line, Tumor; Drug Synergism; Humans; Lung Neoplasms; NAD(P)H Dehydrogenase (Quinone); Naphthoquinones; Sulindac; Up-Regulation |
顯示於: | 解剖學暨細胞生物學科所 |
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