NAMPT inhibition synergizes with NQO1-targeting agents in inducing apoptotic cell death in non-small cell lung cancer cells
| Autor: | Huiying Liu, Haiping Hao, Guangji Wang, Qing-Ran Li, Xuefang Cheng |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Nicotinamide phosphoribosyltransferase Apoptosis FOXO1 Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Carcinoma Non-Small-Cell Lung Cell Line Tumor Drug Discovery NAD(P)H Dehydrogenase (Quinone) Humans Enzyme Inhibitors Nicotinamide Phosphoribosyltransferase chemistry.chemical_classification Nicotinamide General Medicine NAD 030104 developmental biology Enzyme Complementary and alternative medicine chemistry Biochemistry Acetylation 030220 oncology & carcinogenesis Abietanes Cancer research Cytokines NAD+ kinase Naphthoquinones |
| Zdroj: | Chinese Journal of Natural Medicines. 14:582-589 |
| ISSN: | 1875-5364 |
| DOI: | 10.1016/s1875-5364(16)30068-1 |
| Popis: | Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the first rate-limiting step in converting nicotinamide to NAD(+), essential for a number of enzymes and regulatory proteins involved in a variety of cellular processes, including deacetylation enzyme SIRT1 which modulates several tumor suppressors such as p53 and FOXO. Herein we report that NQO1 substrates Tanshione IIA (TSA) and β-lapachone (β-lap) induced a rapid depletion of NAD(+) pool but adaptively a significant upregulation of NAMPT. NAMPT inhibition by FK866 at a nontoxic dose significantly enhanced NQO1-targeting agent-induced apoptotic cell death. Compared with TSA or β-lap treatment alone, co-treatment with FK866 induced a more dramatic depletion of NAD(+), repression of SIRT1 activity, and thereby the increased accumulation of acetylated FOXO1 and the activation of apoptotic pathway. In conclusion, the results from the present study support that NAMPT inhibition can synergize with NQO1 activation to induce apoptotic cell death, thereby providing a new rationale for the development of combinative therapeutic drugs in combating non-small lung cancer. |
| Databáze: | OpenAIRE |
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