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Int. J. Mol. Sci. 2018, 19(2), 447; https://doi.org/10.3390/ijms19020447

Luteolin Inhibits Tumorigenesis and Induces Apoptosis of Non-Small Cell Lung Cancer Cells via Regulation of MicroRNA-34a-5p

Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China
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Received: 28 December 2017 / Revised: 20 January 2018 / Accepted: 29 January 2018 / Published: 2 February 2018
(This article belongs to the Special Issue Alterations to Signalling Pathways in Cancer Cells 2018)
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Abstract

Luteolin (LTL) exerts remarkable tumor suppressive activity on various types of cancers, including non-small cell lung cancer (NSCLC). However, it is not completely understood whether the mechanism of its action against NSCLC is related to microRNAs (miRNAs). In the present study, we investigated the anti-tumor effects of LTL on NSCLC in vitro and in vivo. The results revealed that LTL could inhibit cell proliferation and induce apoptosis in both A549 and H460 cells. In a H460 xenograft tumor model of nude mice, LTL significantly suppressed tumor growth, inhibited cell proliferation, and induced apoptosis. miRNA microarray and quantitative PCR (qPCR) analysis indicated that miR-34a-5p was dramatically upregulated upon LTL treatment in tumor tissues. Furthermore, MDM4 was proved to be a direct target of miR-34a-5p by luciferase reporter gene assay. LTL treatment was associated with increased p53 and p21 protein expressions and decreased MDM4 protein expression in both NSCLC cells and tumor tissues. When miR-34a-5p was inhibited in vitro, the protein expressions of Bcl-2 and MDM4 were recovered, while that of p53, p21, and Bax were attenuated. Moreover, caspase-3 and caspase-9 activation induced by LHL treatment in vitro were also suppressed by miR-34a-5p inhibition. Overall, LTL could inhibit tumorigenesis and induce apoptosis of NSCLC cells by upregulation of miR-34a-5p via targeting MDM4. These findings provide novel insight into the molecular functions of LTL that suggest its potential as a therapeutic agent for human NSCLC. View Full-Text
Keywords: luteolin; apoptosis; non-small cell lung cancer; microRNA-34a-5p luteolin; apoptosis; non-small cell lung cancer; microRNA-34a-5p
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Jiang, Z.-Q.; Li, M.-H.; Qin, Y.-M.; Jiang, H.-Y.; Zhang, X.; Wu, M.-H. Luteolin Inhibits Tumorigenesis and Induces Apoptosis of Non-Small Cell Lung Cancer Cells via Regulation of MicroRNA-34a-5p. Int. J. Mol. Sci. 2018, 19, 447.

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