Mechanism of Urolithin A Inhibiting the Growth of Hepatoma Cells by Regulating Aerobic Glycolysis
10.13748/j.cnki.issn1007-7693.20230499
- VernacularTitle:尿石素A通过调控有氧糖酵解抑制肝癌细胞生长的机制
- Author:
Hongliu HU
1
;
Zhilong HE
2
;
Zhuan WANG
2
;
Lihe JIANG
3
Author Information
1. School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise 533000 , China；Hubei Key Laboratory of Biologic Resources Protection and Utilization, Hubei Minzu University, Enshi 445000 , China
2. College of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China
3. School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise 533000 , China；College of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China；College of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China
- Publication Type:Journal Article
- Keywords:
urolithin； hepatoma； glycolysis； cells growth
- From:
Chinese Journal of Modern Applied Pharmacy
2024;41(8):1047-1055
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE :To explore the molecular mechanism of urolithin A inhibition of human hepatoma cells growth.
METHODS
Hepatoma Huh-7 cells were treated with different concentrations of urolithin A(Uro-A). The inhibition rate of Huh-7 cells survival was detected by CCK-8 assay and the IC50 was calculated. Cell proliferation was detected by colony formation assay and cell migration ability was assessed by cell wound healing experiment. Glucose uptake and lactate level in culture medium through colorimetry and the ATP production in cell through chemiluminescence method was analyzed. Western blotting was applied to detect protein expression levels of glucose transporter(GLUT1), key enzymes of glycolysis(HK2, PFKM, LDHA), p53, p-p38 and Bcl-2 after treatment with different concentrations of Uro-A. Flow cytometry and TUNEL method were used to detect apoptosis rate.
RESULTS
The results of CCK-8 showed that Uro-A significantly inhibited the proliferation of Huh-7 cells, and the IC50 was(48.54±1.21) μmol·L−1. The ability of clone formation and migration decreased after Uro-A treatment. Cellular glucose uptake and level of lactic acid and ATP production were down regulated in Huh-7 cells treated with Uro-A. The results showed that expression of glycolytic key proteins GLUT1, PKM2, LDHA and HK2 decreased. Western Blotting further research indicated that the p53 and p-p38 were activated, while the Bcl-2 was down-regulated. Flow cytometry data and TUNEL method revealed that the induction of apoptosis by Uro-A was remarkably increased.
CONCLUSION
These findings suggest that Uro-A can suppress Huh-7 cell proliferation and migration. The possible mechanism is the inhibition of glycolysis by p53, p-p38 and Bcl-2, which prevent cell growth and finally induce apoptosis.
