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


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


Effect of Phyllanthus amarus Extract on 5-Fluorouracil-Induced Perturbations in Ribonucleotide and Deoxyribonucleotide Pools in HepG2 Cell Line - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

1

State Key Laboratory of Quality Research in Chinese Medicines, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR, China

2

Key Laboratory of Drug Quality Control and Pharmacovigilance Ministry of Education, China Pharmaceutical University, Nanjing 210009, China

3

Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Traditional Medical and Pharmaceutical Sciences, Nanning 530022, China





*

Authors to whom correspondence should be addressed.



Academic Editor: Derek J. McPhee

Abstract 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. View Full-Text

Keywords: Phyllanthus amarus extract; 5-fluorouracil; ribonucleotides; deoxyribonucleotides Phyllanthus amarus extract; 5-fluorouracil; ribonucleotides; deoxyribonucleotides





Autor: Jian-Ru Guo 1, Qian-Qian Chen 1, Christopher Wai-Kei Lam 1, Cai-Yun Wang 1, Feng-Guo Xu 2, Bu-Ming Liu 3,†,* and Wei Zhang 1,†,*

Fuente: http://mdpi.com/



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