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Investigation into perturbed nucleoside metabolism and cell cycle for elucidating the cytotoxicity effect of resveratrol on human lung adenocarcinoma epithelial cells
- Source :
- Chinese journal of natural medicines. 17(8)
- Publication Year :
- 2019
-
Abstract
- In an effort to understand the molecular events contributing to the cytotoxicity activity of resveratrol (RSV), we investigated its effects on human lung adenocarcinoma epithelial cell line A549 at different concentrations. Cellular nucleoside metabolic profiling was determined by an established liquid chromatography-mass spectrometry method in A549 cells. RSV resulted in significant decreases and imbalances of deoxyribonucleoside triphosphates (dNTPs) pools suppressing subsequent DNA synthesis. Meanwhile, RSV at high concentration caused significant cell cycle arrest at S phase, in which cells required the highest dNTPs supply than other phases for DNA replication. The inhibition of DNA synthesis thus blocked subsequent progression through S phase in A549 cells, which may partly contribute to the cytotoxicity effect of RSV. However, hydroxyurea (HU), an inhibitor of RNR activity, caused similar dNTPs perturbation but no S phase arrest, finally no cytotoxicity effect. Therefore, we believed that the dual effect of high concentration RSV, including S phase arrest and DNA synthesis inhibition, was required for its cytotoxicity effect on A549 cells. In summary, our results provided important clues to the molecular basis for the anticancer effect of RSV on epithelial cells.
- Subjects :
- Cell cycle checkpoint
Lung Neoplasms
Cell Survival
Deoxyribonucleotides
Adenocarcinoma of Lung
Resveratrol
01 natural sciences
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Drug Discovery
Humans
Hydroxyurea
Cytotoxicity
A549 cell
DNA synthesis
Dose-Response Relationship, Drug
010405 organic chemistry
Chemistry
Cell Cycle
DNA replication
Epithelial Cells
General Medicine
respiratory system
Cell cycle
0104 chemical sciences
Cell biology
Deoxyribonucleoside
Complementary and alternative medicine
A549 Cells
030220 oncology & carcinogenesis
S Phase Cell Cycle Checkpoints
Subjects
Details
- ISSN :
- 18755364
- Volume :
- 17
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Chinese journal of natural medicines
- Accession number :
- edsair.doi.dedup.....2b51b407f05a16e1e7185dcead15f7d9