Licochalcone A inhibits hypoxia-inducible factor-1α accumulation by suppressing mitochondrial respiration in hypoxic cancer cells - 19/12/20
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Graphical abstract |
Highlights |
• | Hypoxia-inducible factor (HIF)-1 regulates the cellular response in hypoxic tumors. |
• | Glycyrrhiza uralensis exerts HIF-1 inhibitory activity in hypoxic cancer cells. |
• | Licochalcone A suppresses HIF-1α accumulation and expression of its target genes. |
• | Licochalcone A reduces ATP production, suppressing cancer cell proliferation. |
• | Licochalcone A has therapeutic potential as an anticancer agent. |
Abstract |
Hypoxia-inducible factor (HIF)-1 is an important regulator of the cellular response in the hypoxic tumor environment. While searching for HIF inhibitors derived from natural products that act as anticancer agents, we found that Glycyrrhiza uralensis exerts HIF-1 inhibitory activity in hypoxic cancer cells. Among the five components of G. uralensis, licochalcone A was found to potently suppress hypoxia-induced HIF-1α accumulation and expression of HIF-1α target genes, including GLUT1 and PDK1 in HCT116 cells. Licochalcone A also enhances intracellular oxygen content by directly inhibiting mitochondrial respiration, resulting in oxygen-dependent HIF-1α degradation. Hence, licochalcone A may effectively inhibit ATP production, primarily by reducing the mitochondrial respiration-mediated ATP production rate rather than the glycolysis-mediated ATP production rate. This effect subsequently suppresses cancer cell viability, including that of HCT116, H1299, and H322 cells. Consequently, these results suggest that licochalcone A has therapeutic potential in hypoxic cancer cells.
Le texte complet de cet article est disponible en PDF.Abbreviations : BNDF, DMSO, ECAR, EdU, GAPDH, GLUT1, HIF-1, HRE, IL, iNOS, LPS, OCR, PCR, PDK, PVDF, ROS, TNFα, TrkB, VEGF
Keywords : Licochalcone A, Hypoxia, Hypoxia-inducible factor, Mitochondria, Cancer metabolism
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Vol 133
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