Cargando…

Effect of Phyllanthus amarus Extract on 5-Fluorouracil-Induced Perturbations in Ribonucleotide and Deoxyribonucleotide Pools in HepG2 Cell Line

The aim of this study was to investigate the antitumor activities of Phyllanthus amarus (PHA) and its potential of herb–drug interactions with 5-Fluorouracil (5-FU). Cell viability, ribonucleotides (RNs) and deoxyribonucleotides (dRNs) levels, cell cycle distribution, and expression of thymidylate s...

Descripción completa

Detalles Bibliográficos
Autores principales: Guo, Jian-Ru, Chen, Qian-Qian, Lam, Christopher Wai-Kei, Wang, Cai-Yun, Xu, Feng-Guo, Liu, Bu-Ming, Zhang, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273671/
https://www.ncbi.nlm.nih.gov/pubmed/27657029
http://dx.doi.org/10.3390/molecules21091254
_version_ 1783377441148895232
author Guo, Jian-Ru
Chen, Qian-Qian
Lam, Christopher Wai-Kei
Wang, Cai-Yun
Xu, Feng-Guo
Liu, Bu-Ming
Zhang, Wei
author_facet Guo, Jian-Ru
Chen, Qian-Qian
Lam, Christopher Wai-Kei
Wang, Cai-Yun
Xu, Feng-Guo
Liu, Bu-Ming
Zhang, Wei
author_sort Guo, Jian-Ru
collection PubMed
description The aim of this study was to investigate the antitumor activities of Phyllanthus amarus (PHA) and its potential of herb–drug interactions with 5-Fluorouracil (5-FU). Cell viability, ribonucleotides (RNs) and deoxyribonucleotides (dRNs) levels, cell cycle distribution, and expression of thymidylate synthase (TS) and ribonucleotide reductase (RR) proteins were measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, high performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS) method, flow cytometry and Western blot analysis, respectively. Our standardized PHA extract showed toxicity to HepG2 cells at high concentrations after 72 h exposure and induced G2/M cell cycle arrest. Combined use of 5-FU with PHA resulted in significant decreases in ATP, CTP, GTP, UTP and dTTP levels, while AMP, CMP, GMP and dUMP levels increased significantly compared with use of 5-FU alone. Further, PHA could increase the role of cell cycle arrest at S phase induced by 5-FU. Although PHA alone had no direct impact on TS and RR, PHA could change the levels of RNs and dRNs when combined with 5-FU. This may be due to cell cycle arrest or regulation of key enzyme steps in intracellular RNs and dRNs metabolism.
format Online
Article
Text
id pubmed-6273671
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-62736712018-12-28 Effect of Phyllanthus amarus Extract on 5-Fluorouracil-Induced Perturbations in Ribonucleotide and Deoxyribonucleotide Pools in HepG2 Cell Line Guo, Jian-Ru Chen, Qian-Qian Lam, Christopher Wai-Kei Wang, Cai-Yun Xu, Feng-Guo Liu, Bu-Ming Zhang, Wei Molecules Article The aim of this study was to investigate the antitumor activities of Phyllanthus amarus (PHA) and its potential of herb–drug interactions with 5-Fluorouracil (5-FU). Cell viability, ribonucleotides (RNs) and deoxyribonucleotides (dRNs) levels, cell cycle distribution, and expression of thymidylate synthase (TS) and ribonucleotide reductase (RR) proteins were measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, high performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS) method, flow cytometry and Western blot analysis, respectively. Our standardized PHA extract showed toxicity to HepG2 cells at high concentrations after 72 h exposure and induced G2/M cell cycle arrest. Combined use of 5-FU with PHA resulted in significant decreases in ATP, CTP, GTP, UTP and dTTP levels, while AMP, CMP, GMP and dUMP levels increased significantly compared with use of 5-FU alone. Further, PHA could increase the role of cell cycle arrest at S phase induced by 5-FU. Although PHA alone had no direct impact on TS and RR, PHA could change the levels of RNs and dRNs when combined with 5-FU. This may be due to cell cycle arrest or regulation of key enzyme steps in intracellular RNs and dRNs metabolism. MDPI 2016-09-20 /pmc/articles/PMC6273671/ /pubmed/27657029 http://dx.doi.org/10.3390/molecules21091254 Text en © 2016 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Guo, Jian-Ru
Chen, Qian-Qian
Lam, Christopher Wai-Kei
Wang, Cai-Yun
Xu, Feng-Guo
Liu, Bu-Ming
Zhang, Wei
Effect of Phyllanthus amarus Extract on 5-Fluorouracil-Induced Perturbations in Ribonucleotide and Deoxyribonucleotide Pools in HepG2 Cell Line
title Effect of Phyllanthus amarus Extract on 5-Fluorouracil-Induced Perturbations in Ribonucleotide and Deoxyribonucleotide Pools in HepG2 Cell Line
title_full Effect of Phyllanthus amarus Extract on 5-Fluorouracil-Induced Perturbations in Ribonucleotide and Deoxyribonucleotide Pools in HepG2 Cell Line
title_fullStr Effect of Phyllanthus amarus Extract on 5-Fluorouracil-Induced Perturbations in Ribonucleotide and Deoxyribonucleotide Pools in HepG2 Cell Line
title_full_unstemmed Effect of Phyllanthus amarus Extract on 5-Fluorouracil-Induced Perturbations in Ribonucleotide and Deoxyribonucleotide Pools in HepG2 Cell Line
title_short Effect of Phyllanthus amarus Extract on 5-Fluorouracil-Induced Perturbations in Ribonucleotide and Deoxyribonucleotide Pools in HepG2 Cell Line
title_sort effect of phyllanthus amarus extract on 5-fluorouracil-induced perturbations in ribonucleotide and deoxyribonucleotide pools in hepg2 cell line
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273671/
https://www.ncbi.nlm.nih.gov/pubmed/27657029
http://dx.doi.org/10.3390/molecules21091254
work_keys_str_mv AT guojianru effectofphyllanthusamarusextracton5fluorouracilinducedperturbationsinribonucleotideanddeoxyribonucleotidepoolsinhepg2cellline
AT chenqianqian effectofphyllanthusamarusextracton5fluorouracilinducedperturbationsinribonucleotideanddeoxyribonucleotidepoolsinhepg2cellline
AT lamchristopherwaikei effectofphyllanthusamarusextracton5fluorouracilinducedperturbationsinribonucleotideanddeoxyribonucleotidepoolsinhepg2cellline
AT wangcaiyun effectofphyllanthusamarusextracton5fluorouracilinducedperturbationsinribonucleotideanddeoxyribonucleotidepoolsinhepg2cellline
AT xufengguo effectofphyllanthusamarusextracton5fluorouracilinducedperturbationsinribonucleotideanddeoxyribonucleotidepoolsinhepg2cellline
AT liubuming effectofphyllanthusamarusextracton5fluorouracilinducedperturbationsinribonucleotideanddeoxyribonucleotidepoolsinhepg2cellline
AT zhangwei effectofphyllanthusamarusextracton5fluorouracilinducedperturbationsinribonucleotideanddeoxyribonucleotidepoolsinhepg2cellline