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Gambogic acid suppresses hypoxia-induced hypoxia-inducible factor-1α/vascular endothelial growth factor expression via inhibiting phosphatidylinositol 3-kinase/Akt/mammalian target protein of rapamycin pathway in multiple myeloma cells.

Wang F, Zhang W, Guo L, Bao W, Jin N, Liu R, Liu P, Wang Y, Guo Q, Chen B - Cancer Sci. (2014)

Bottom Line: We found that hypoxia induced increase in the level of HIF-1α subunit protein and activated the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target protein of rapamycin (mTOR) pathway.Mechanistic studies exhibited that GA inhibited the production of HIF-1α by reducing phosphorylation of Akt and mTOR in U266 cells.Taken together, our results identify that GA suppresses hypoxia-activated pathways that are linked to MM progression, at least partly, by the inhibition of the PI3K/Akt/mTOR signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), Medical School, Zhongda Hospital, Southeast University, Nanjing, China.

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Effect of gambogic acid (GA) on the secretion and expression of vascular endothelial growth factor (VEGF) in U266 cells under normoxia and hypoxia. (a) U266 cells were treated by GA (0, 0.05, 0.1, and 0.2 μM) for 8 h under normoxia and hypoxia. VEGF secretion was detected by ELISA assay. Bars were the mean ± SD (n = 3). The comparisons were made relative to untreated controls, and the different levels of significance were indicated as *P < 0.05 and **P < 0.01. (b) Effect of GA on VEGF mRNA level under normoxia and hypoxia. U266 cells were treated with various concentrations of GA (0, 0.05, 0.1, and 0.2 μM) for 4 h under normoxic and hypoxic conditions. VEGF mRNA was detected by real-time polymerase chain reaction (PCR) and analyzed by the ΔΔCt method. Bars were shown as mean ± SD (n = 3) and represent VEGF/β-actin fold relative to the untreated group. The different levels of significance were indicated as *P < 0.05 and **P < 0.01. (c) Effect of GA on VEGF protein expression under normoxia and hypoxia. U266 cells were treated with various concentrations of GA (0, 0.05, 0.1, and 0.2 μM) for 4 h under normoxic and hypoxic conditions. VEGF protein expression was analyzed by western blots. (d) For quantity of (c), images were analyzed using Image J. Bars are the mean ± SD (n = 3). The comparisons were made relative to hypoxia alone group, and the different levels of significance were indicated as *P < 0.05 and **P < 0.01.
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fig02: Effect of gambogic acid (GA) on the secretion and expression of vascular endothelial growth factor (VEGF) in U266 cells under normoxia and hypoxia. (a) U266 cells were treated by GA (0, 0.05, 0.1, and 0.2 μM) for 8 h under normoxia and hypoxia. VEGF secretion was detected by ELISA assay. Bars were the mean ± SD (n = 3). The comparisons were made relative to untreated controls, and the different levels of significance were indicated as *P < 0.05 and **P < 0.01. (b) Effect of GA on VEGF mRNA level under normoxia and hypoxia. U266 cells were treated with various concentrations of GA (0, 0.05, 0.1, and 0.2 μM) for 4 h under normoxic and hypoxic conditions. VEGF mRNA was detected by real-time polymerase chain reaction (PCR) and analyzed by the ΔΔCt method. Bars were shown as mean ± SD (n = 3) and represent VEGF/β-actin fold relative to the untreated group. The different levels of significance were indicated as *P < 0.05 and **P < 0.01. (c) Effect of GA on VEGF protein expression under normoxia and hypoxia. U266 cells were treated with various concentrations of GA (0, 0.05, 0.1, and 0.2 μM) for 4 h under normoxic and hypoxic conditions. VEGF protein expression was analyzed by western blots. (d) For quantity of (c), images were analyzed using Image J. Bars are the mean ± SD (n = 3). The comparisons were made relative to hypoxia alone group, and the different levels of significance were indicated as *P < 0.05 and **P < 0.01.

Mentions: We examined VEGF expression and secretion from the U266 cells under normoxia and hypoxia and the effect of GA on that. The results showed that VEGF was more secreted under hypoxia and GA decreased VEGF secretion compared to the control group under hypoxia much more significantly than under normoxia (Fig. 2a).


Gambogic acid suppresses hypoxia-induced hypoxia-inducible factor-1α/vascular endothelial growth factor expression via inhibiting phosphatidylinositol 3-kinase/Akt/mammalian target protein of rapamycin pathway in multiple myeloma cells.

Wang F, Zhang W, Guo L, Bao W, Jin N, Liu R, Liu P, Wang Y, Guo Q, Chen B - Cancer Sci. (2014)

Effect of gambogic acid (GA) on the secretion and expression of vascular endothelial growth factor (VEGF) in U266 cells under normoxia and hypoxia. (a) U266 cells were treated by GA (0, 0.05, 0.1, and 0.2 μM) for 8 h under normoxia and hypoxia. VEGF secretion was detected by ELISA assay. Bars were the mean ± SD (n = 3). The comparisons were made relative to untreated controls, and the different levels of significance were indicated as *P < 0.05 and **P < 0.01. (b) Effect of GA on VEGF mRNA level under normoxia and hypoxia. U266 cells were treated with various concentrations of GA (0, 0.05, 0.1, and 0.2 μM) for 4 h under normoxic and hypoxic conditions. VEGF mRNA was detected by real-time polymerase chain reaction (PCR) and analyzed by the ΔΔCt method. Bars were shown as mean ± SD (n = 3) and represent VEGF/β-actin fold relative to the untreated group. The different levels of significance were indicated as *P < 0.05 and **P < 0.01. (c) Effect of GA on VEGF protein expression under normoxia and hypoxia. U266 cells were treated with various concentrations of GA (0, 0.05, 0.1, and 0.2 μM) for 4 h under normoxic and hypoxic conditions. VEGF protein expression was analyzed by western blots. (d) For quantity of (c), images were analyzed using Image J. Bars are the mean ± SD (n = 3). The comparisons were made relative to hypoxia alone group, and the different levels of significance were indicated as *P < 0.05 and **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig02: Effect of gambogic acid (GA) on the secretion and expression of vascular endothelial growth factor (VEGF) in U266 cells under normoxia and hypoxia. (a) U266 cells were treated by GA (0, 0.05, 0.1, and 0.2 μM) for 8 h under normoxia and hypoxia. VEGF secretion was detected by ELISA assay. Bars were the mean ± SD (n = 3). The comparisons were made relative to untreated controls, and the different levels of significance were indicated as *P < 0.05 and **P < 0.01. (b) Effect of GA on VEGF mRNA level under normoxia and hypoxia. U266 cells were treated with various concentrations of GA (0, 0.05, 0.1, and 0.2 μM) for 4 h under normoxic and hypoxic conditions. VEGF mRNA was detected by real-time polymerase chain reaction (PCR) and analyzed by the ΔΔCt method. Bars were shown as mean ± SD (n = 3) and represent VEGF/β-actin fold relative to the untreated group. The different levels of significance were indicated as *P < 0.05 and **P < 0.01. (c) Effect of GA on VEGF protein expression under normoxia and hypoxia. U266 cells were treated with various concentrations of GA (0, 0.05, 0.1, and 0.2 μM) for 4 h under normoxic and hypoxic conditions. VEGF protein expression was analyzed by western blots. (d) For quantity of (c), images were analyzed using Image J. Bars are the mean ± SD (n = 3). The comparisons were made relative to hypoxia alone group, and the different levels of significance were indicated as *P < 0.05 and **P < 0.01.
Mentions: We examined VEGF expression and secretion from the U266 cells under normoxia and hypoxia and the effect of GA on that. The results showed that VEGF was more secreted under hypoxia and GA decreased VEGF secretion compared to the control group under hypoxia much more significantly than under normoxia (Fig. 2a).

Bottom Line: We found that hypoxia induced increase in the level of HIF-1α subunit protein and activated the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target protein of rapamycin (mTOR) pathway.Mechanistic studies exhibited that GA inhibited the production of HIF-1α by reducing phosphorylation of Akt and mTOR in U266 cells.Taken together, our results identify that GA suppresses hypoxia-activated pathways that are linked to MM progression, at least partly, by the inhibition of the PI3K/Akt/mTOR signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), Medical School, Zhongda Hospital, Southeast University, Nanjing, China.

Show MeSH
Related in: MedlinePlus