Investigation into perturbed nucleoside metabolism and cell cycle for elucidating the cytotoxicity effect of resveratrol on human lung adenocarcinoma epithelial cells.
10.1016/S1875-5364(19)30063-9
- Author:
Zheng LI
1
;
Qian-Qian CHEN
1
;
Christopher Wai Kei LAM
2
;
Jian-Ru GUO
1
;
Wei-Jia ZHANG
3
;
Cai-Yun WANG
1
;
Vincent Kam Wai WONG
1
;
Mei-Cun YAO
4
;
Wei ZHANG
5
Author Information
1. State Key Laboratory of Quality Research in Chinese Medicines and Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau 999078, China.
2. Faculty of Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau 999078, China.
3. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
4. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: Yaomeicun@gmail.com.
5. State Key Laboratory of Quality Research in Chinese Medicines and Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau 999078, China. Electronic address: Wzhang@must.edu.mo.
- Publication Type:Journal Article
- Keywords:
DNA synthesis;
Deoxyribonucleotides;
LC-MS;
Resveratrol;
S phase arrest
- From:
Chinese Journal of Natural Medicines (English Ed.)
2019;17(8):608-615
- CountryChina
- Language:English
-
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.
