Cell metabolomics study of ginkgo flavone aglycone combined with doxorubicin against liver cancer in synergy.
10.19540/j.cnki.cjcmm.20220506.401
- Author:
Yuan LU
1
;
Yan-Li WANG
2
;
Zhong-Jun SONG
2
;
Xiao-Qing ZHU
2
;
Chun-Hua LIU
3
;
Ji-Yu CHEN
4
;
Yong-Jun LI
3
;
Yan HE
4
Author Information
1. Clinical Trial Research Center, the Affiliated Hospital of Guizhou Medical University Guiyang 550001, China Provincial Key Laboratory of Pharmaceutics in Guizhou Province, State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University Guiyang 550004, China.
2. School of Pharmaceutical Sciences, Guizhou Medical University Guiyang 550004, China.
3. Engineering Research Center for the Development and Application of Ethnic Medicine and Traditional Chinese Medicine (Ministry of Education), Guizhou Medical University Guiyang 550004, China.
4. Clinical Trial Research Center, the Affiliated Hospital of Guizhou Medical University Guiyang 550001, China.
- Publication Type:Journal Article
- Keywords:
H22 cell;
cell metabolomics;
doxorubicin;
ginkgo flavone aglycone;
hepatocellular carcinoma;
synergy
- MeSH:
Arginine/therapeutic use*;
Doxorubicin/therapeutic use*;
Flavones/therapeutic use*;
Ginkgo biloba/chemistry*;
Glutathione;
Humans;
Isoleucine/therapeutic use*;
Leucine/therapeutic use*;
Liver Neoplasms/drug therapy*;
Metabolomics/methods*;
Phenylalanine/therapeutic use*;
Proline;
Tandem Mass Spectrometry/methods*;
Tyrosine/therapeutic use*;
Valine/therapeutic use*;
beta-Alanine/therapeutic use*
- From:
China Journal of Chinese Materia Medica
2022;47(18):5040-5051
- CountryChina
- Language:Chinese
-
Abstract:
Ultra-high-performance liquid chromatography-Q exactive orbitrap tandem mass spectrometry(UHPLC-QEOrbitrap-MS/MS) was used to explore the inhibitory effect and mechanism of ginkgo flavone aglycone(GA) combined with doxorubicin(DOX) on H22 cells. The effects of different concentrations of GA and DOX on the viability of H22 cells were investigated, and combination index(CI) was used to evaluate the effects. In the experiments, control(CON) group, DOX group, GA group, and combined GA and DOX(GDOX) group were constructed. Then the metabolomics strategy was employed to explore the metabolic markers that were significantly changed after combination therapy on the basis of single medication treatment, and by analyzing their biological significance, the effect and mechanism of the anti-tumor effect of GA combined with DOX were explained. The results revealed that when 30 μg·mL~(-1) GA and 0.5 μmol·L~(-1) DOX was determined as the co-administration concentration, the CI value was 0.808, indicating that the combination of GA and DOX had a synergistic anti-tumor effect. Metabolomics analysis identified 23 metabolic markers, including L-arginine, L-tyrosine and L-valine, mostly amino acids. Compared with the CON group, 22 and 17 metabolic markers were significantly down-regulated after DOX treatment and GA treatment, respectively. Compared with the DOX and GA groups, the treatment of GA combined with DOX further down-regulated the levels of these metabolic markers in liver cancer, which might contribute to the synergistic effect of the two. Five key metabolic pathways were found in pathway enrichment analysis, including glutathione metabolism, phenylalanine metabolism, arginine and proline metabolism, β-alanine metabolism, and valine, leucine and isoleucine degradation. These findings demonstrated that the combination of GA and DOX remarkably inhibited the viability of H22 cells and exerted a synergistic anti-tumor effect. The mechanism might be related to the influence of the energy supply of tumor cells by interfering with the metabolism of various amino acids.
