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Oroxylin A regulates glucose metabolism in response to hypoxic stress with the involvement of Hypoxia-inducible factor-1 in human hepatoma HepG2 cells.
- Source :
-
Molecular carcinogenesis [Mol Carcinog] 2016 Aug; Vol. 55 (8), pp. 1275-89. Date of Electronic Publication: 2015 Aug 10. - Publication Year :
- 2016
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Abstract
- Metabolic alteration in cancer cells is one of the most conspicuous characteristics that distinguish cancer cells from normal cells. In this study, we investigated the influence and signaling ways of oroxylin A affecting cancer cell energy metabolism under hypoxia. The data showed that oroxylin A remarkably reduced the generation of lactate and glucose uptake under hypoxia in HepG2 cells. Moreover, oroxylin A inhibited HIF-1α expression and its stability. The downstream targets (PDK1, LDHA, and HK II), as well as their mRNA levels were also suppressed by oroxylin A under hypoxia. The silencing or the overexpression of HIF-1α assays suggested that HIF-1α is required for metabolic effect of oroxylin A in HepG2 cells during hypoxia. Furthermore, oroxylin A could reduce the expression of complex III in mitochondrial respiratory chain, and then decrease the accumulation of ROS at moderate concentrations (0-50 µM) under hypoxia, which was benefit for its inhibition on glycolytic activity by decreasing ROS-mediated HIF-1 expression. Besides, oroxylin A didn't cause the loss of MMP under hypoxia and had no obvious effects on the expression of OXPHOS complexes, suggesting that oroxylin A did not affect mitochondrial mass at the moderate stress of oroxylin A. The suppressive effect of oroxylin A on glycolysis led to a significantly repress of ATP generation, for ATP generation mostly depends on glycolysis in HepG2 cells. This study revealed a new aspect of glucose metabolism regulation of oroxylin A under hypoxia, which may contribute to its new anticancer mechanism. © 2015 Wiley Periodicals, Inc.<br /> (© 2015 Wiley Periodicals, Inc.)
- Subjects :
- Carcinoma, Hepatocellular drug therapy
Cell Hypoxia drug effects
Energy Metabolism drug effects
Gene Expression Regulation, Neoplastic drug effects
Glucose metabolism
Hep G2 Cells
Humans
Lactic Acid metabolism
Liver Neoplasms drug therapy
Reactive Oxygen Species metabolism
Signal Transduction drug effects
Carcinoma, Hepatocellular metabolism
Flavonoids pharmacology
Glycolysis drug effects
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Liver Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-2744
- Volume :
- 55
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Molecular carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 26259145
- Full Text :
- https://doi.org/10.1002/mc.22369