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

Autor: Xu Zhang, Yue-Mu Qin, Mu-Han Li, Ze-Qun Jiang, Hai-Ying Jiang, Mian-Hua Wu
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Lung Neoplasms
Carcinogenesis
Cell Cycle Proteins
medicine.disease_cause
luteolin
apoptosis
non-small cell lung cancer
microRNA-34a-5p
lcsh:Chemistry
Mice
0302 clinical medicine
Carcinoma
Non-Small-Cell Lung
Nuclear protein
lcsh:QH301-705.5
Spectroscopy
bcl-2-Associated X Protein
biology
Chemistry
Nuclear Proteins
General Medicine
Tumor Burden
Computer Science Applications
Gene Expression Regulation
Neoplastic
Proto-Oncogene Proteins c-bcl-2
Caspases
030220 oncology & carcinogenesis
Cyclin-Dependent Kinase Inhibitor p21
Cell Survival
Mice
Nude
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
Bcl-2-associated X protein
Downregulation and upregulation
Cell Line
Tumor
Proto-Oncogene Proteins
microRNA
medicine
Animals
Humans
Physical and Theoretical Chemistry
Molecular Biology
Cell growth
Gene Expression Profiling
Organic Chemistry
Microarray Analysis
Antineoplastic Agents
Phytogenic
Xenograft Model Antitumor Assays
respiratory tract diseases
MicroRNAs
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
MicroRNA 34a
Apoptosis
biology.protein
Cancer research
Tumor Suppressor Protein p53
Zdroj: International Journal of Molecular Sciences, Vol 19, Iss 2, p 447 (2018)
International Journal of Molecular Sciences; Volume 19; Issue 2; Pages: 447
International Journal of Molecular Sciences
ISSN: 1422-0067
DOI: 10.3390/ijms19020447
Popis: 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.
Databáze: OpenAIRE
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