5-demethylnobiletin promotes the formation of polymerized tubulin, leads to G2/M phase arrest and induces autophagy via JNK activation in human lung cancer cells

The Journal of Nutritional Biochemistry
Yu-Kuo ChenChi-Chen Lin

Abstract

5-Demethylnobiletin is a hydroxylated polymethoxyflavone found in citrus plants that shows antiproliferative activities in several cancer cell lines. In this study, we investigated the effects and underlying molecular mechanisms of 5-demethylnobiletin on inhibition of cell growth, apoptosis, cell cycle and autophagy in A549 and CL1-5 lung cancer cells. The results of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay suggested that 5-demethylnobiletin inhibited cell growth in a dose- and time-dependent manner. Flow cytometry results suggested that 5-demethylnobiletin inhibited proliferation in lung cancer cells by inducing G2/M cell cycle phase arrest but predominantly not through apoptosis. Western blot results illustrated that the blockade of the cell cycle was associated with reduced levels of cdc25 and cdc2. Notably, our results indicated that 5-demethylnobiletin induced significant abnormal microtubule dynamics in A549 and CL1-5 cells, a novel finding. Studies conducted with isolated tubulin and docking models suggest that 5-demethylnobiletin promoted the polymerization of microtubules and bound to the taxol site. Additionally, 5-demethylnobiletin might also induce autophagy via activation of the JNK si...Continue Reading

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Citations

May 25, 2016·Journal of Agricultural and Food Chemistry·Mingyue SongHang Xiao
Feb 12, 2020·Medicinal Research Reviews·Vibhuti JoshiAmit Mishra
Sep 16, 2020·International Journal of Molecular Sciences·Monica BenvenutoRoberto Bei
Nov 28, 2020·Bioorganic & Medicinal Chemistry Letters·Hui-Chi HuangMing-Kuem Lin

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