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Quercetin reduces cyclin D1 activity and induces G1 phase arrest in HepG2 cells
Quercetin is able to inhibit proliferation of malignant tumor cells; however, the exact mechanism involved in this biological process remains unclear. The current study utilized a quantitative proteomic analysis to explore the antitumor mechanisms of quercetin. The leucine of HepG2 cells treated wit...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4906932/ https://www.ncbi.nlm.nih.gov/pubmed/27347174 http://dx.doi.org/10.3892/ol.2016.4639 |
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author | ZHOU, JIN LI, LU FANG, LI XIE, HUA YAO, WENXIU ZHOU, XIANG XIONG, ZHUJUAN WANG, LI LI, ZHIXI LUO, FENG |
author_facet | ZHOU, JIN LI, LU FANG, LI XIE, HUA YAO, WENXIU ZHOU, XIANG XIONG, ZHUJUAN WANG, LI LI, ZHIXI LUO, FENG |
author_sort | ZHOU, JIN |
collection | PubMed |
description | Quercetin is able to inhibit proliferation of malignant tumor cells; however, the exact mechanism involved in this biological process remains unclear. The current study utilized a quantitative proteomic analysis to explore the antitumor mechanisms of quercetin. The leucine of HepG2 cells treated with quercetin was labeled as d3 by stable isotope labeling by amino acids in cell culture (SILAC). The isotope peaks of control HepG2 cells were compared with the d3-labeled HepG2 cells by mass spectrometry (MS) to identify significantly altered proteins. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analyses were subsequently employed to verify the results of the MS analysis. A flow cytometry assay was designed to observe the influence of various quercetin treatment concentrations on the cell cycle distribution of HepG2 cells. The results indicated that quercetin is able to substantially inhibit proliferation of HepG2 cells and induce an obvious morphological alteration of cells. According to the MS results, the 70 credibly-changed proteins that were identified may play important roles in multiple cellular processes, including protein synthesis, signaling, cytoskeletal processes and metabolism. Among these functional proteins, the expression of cyclin D1 (CCND1) was found to be significantly decreased. RT-PCR and western blot analyses verified the SILAC-MS results of decreased CCND1 expression. In summary, flow cytometry revealed that quercetin is able to induce G1 phase arrest in HepG2 cells. Based on the aforementioned observations, it is suggested that quercetin exerts antitumor activity in HepG2 cells through multiple pathways, including interfering with CCND1 gene expression to disrupt the cell cycle and proliferation of HepG2 cells. In the future, we aim to explore this effect in vivo. |
format | Online Article Text |
id | pubmed-4906932 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-49069322016-06-24 Quercetin reduces cyclin D1 activity and induces G1 phase arrest in HepG2 cells ZHOU, JIN LI, LU FANG, LI XIE, HUA YAO, WENXIU ZHOU, XIANG XIONG, ZHUJUAN WANG, LI LI, ZHIXI LUO, FENG Oncol Lett Articles Quercetin is able to inhibit proliferation of malignant tumor cells; however, the exact mechanism involved in this biological process remains unclear. The current study utilized a quantitative proteomic analysis to explore the antitumor mechanisms of quercetin. The leucine of HepG2 cells treated with quercetin was labeled as d3 by stable isotope labeling by amino acids in cell culture (SILAC). The isotope peaks of control HepG2 cells were compared with the d3-labeled HepG2 cells by mass spectrometry (MS) to identify significantly altered proteins. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analyses were subsequently employed to verify the results of the MS analysis. A flow cytometry assay was designed to observe the influence of various quercetin treatment concentrations on the cell cycle distribution of HepG2 cells. The results indicated that quercetin is able to substantially inhibit proliferation of HepG2 cells and induce an obvious morphological alteration of cells. According to the MS results, the 70 credibly-changed proteins that were identified may play important roles in multiple cellular processes, including protein synthesis, signaling, cytoskeletal processes and metabolism. Among these functional proteins, the expression of cyclin D1 (CCND1) was found to be significantly decreased. RT-PCR and western blot analyses verified the SILAC-MS results of decreased CCND1 expression. In summary, flow cytometry revealed that quercetin is able to induce G1 phase arrest in HepG2 cells. Based on the aforementioned observations, it is suggested that quercetin exerts antitumor activity in HepG2 cells through multiple pathways, including interfering with CCND1 gene expression to disrupt the cell cycle and proliferation of HepG2 cells. In the future, we aim to explore this effect in vivo. D.A. Spandidos 2016-07 2016-05-27 /pmc/articles/PMC4906932/ /pubmed/27347174 http://dx.doi.org/10.3892/ol.2016.4639 Text en Copyright: © Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles ZHOU, JIN LI, LU FANG, LI XIE, HUA YAO, WENXIU ZHOU, XIANG XIONG, ZHUJUAN WANG, LI LI, ZHIXI LUO, FENG Quercetin reduces cyclin D1 activity and induces G1 phase arrest in HepG2 cells |
title | Quercetin reduces cyclin D1 activity and induces G1 phase arrest in HepG2 cells |
title_full | Quercetin reduces cyclin D1 activity and induces G1 phase arrest in HepG2 cells |
title_fullStr | Quercetin reduces cyclin D1 activity and induces G1 phase arrest in HepG2 cells |
title_full_unstemmed | Quercetin reduces cyclin D1 activity and induces G1 phase arrest in HepG2 cells |
title_short | Quercetin reduces cyclin D1 activity and induces G1 phase arrest in HepG2 cells |
title_sort | quercetin reduces cyclin d1 activity and induces g1 phase arrest in hepg2 cells |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4906932/ https://www.ncbi.nlm.nih.gov/pubmed/27347174 http://dx.doi.org/10.3892/ol.2016.4639 |
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