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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: Gambogic acid (GA) is the major active ingredient of gamboge, which has been shown to possess antitumor effect by in vitro and in vivo study.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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Related in: MedlinePlus

Gambogic acid (GA) inhibited tumor angiogenesis in U266 xenograft mouse model. (a) Immunohistochemistry was performed in tumor sections with antibodies of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and CD31. The result showed a remarkable decrease in expression of HIF-1α, VEGF and CD31 in the treated groups with 2 and 4 mg/kg GA compared with untreated control groups. (b) To identify the tumor angiogenesis, the stained area of CD31 in 10 fields was quantified by using Image Pro Plus. Bars are the mean ± SD (n = 10). The comparisons were made relative to untreated controls, and the different levels of significance was indicated as **P < 0.01. (c) The images were quantified using Image Pro Plus and mean optical densities (of control) of VEGF and HIF-1α were shown. Bars are the mean ± SD (n = 10). The comparisons were made relative to untreated controls, and the different levels of significance was indicated as **P < 0.01.
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fig06: Gambogic acid (GA) inhibited tumor angiogenesis in U266 xenograft mouse model. (a) Immunohistochemistry was performed in tumor sections with antibodies of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and CD31. The result showed a remarkable decrease in expression of HIF-1α, VEGF and CD31 in the treated groups with 2 and 4 mg/kg GA compared with untreated control groups. (b) To identify the tumor angiogenesis, the stained area of CD31 in 10 fields was quantified by using Image Pro Plus. Bars are the mean ± SD (n = 10). The comparisons were made relative to untreated controls, and the different levels of significance was indicated as **P < 0.01. (c) The images were quantified using Image Pro Plus and mean optical densities (of control) of VEGF and HIF-1α were shown. Bars are the mean ± SD (n = 10). The comparisons were made relative to untreated controls, and the different levels of significance was indicated as **P < 0.01.

Mentions: To confirm the macroscopic observations and address the potential effect of GA in vivo, immunohistochemistry was performed. The results showed that the presence of endothelial-specific antibody CD31-stained capillaries in xenografts was dose-dependently reduced by GA treatment (Fig. 6a,b), suggesting GA attenuated the tumor angiogenesis. To investigate whether the anti-angiogenesis effect of GA was due to the decreased level of VEGF and HIF-1α, immunohistochemistry for VEGF and HIF-1α was performed. The same as CD31, the tumor sections treated with GA showed significantly lower levels of VEGF and HIF-1α than that of control tumor tissue (Fig. 6a,c). These results further supported that GA, a HIF-1α inhibitor, is a potential compound for MM therapy.


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)

Gambogic acid (GA) inhibited tumor angiogenesis in U266 xenograft mouse model. (a) Immunohistochemistry was performed in tumor sections with antibodies of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and CD31. The result showed a remarkable decrease in expression of HIF-1α, VEGF and CD31 in the treated groups with 2 and 4 mg/kg GA compared with untreated control groups. (b) To identify the tumor angiogenesis, the stained area of CD31 in 10 fields was quantified by using Image Pro Plus. Bars are the mean ± SD (n = 10). The comparisons were made relative to untreated controls, and the different levels of significance was indicated as **P < 0.01. (c) The images were quantified using Image Pro Plus and mean optical densities (of control) of VEGF and HIF-1α were shown. Bars are the mean ± SD (n = 10). The comparisons were made relative to untreated controls, and the different levels of significance was indicated as **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4317858&req=5

fig06: Gambogic acid (GA) inhibited tumor angiogenesis in U266 xenograft mouse model. (a) Immunohistochemistry was performed in tumor sections with antibodies of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and CD31. The result showed a remarkable decrease in expression of HIF-1α, VEGF and CD31 in the treated groups with 2 and 4 mg/kg GA compared with untreated control groups. (b) To identify the tumor angiogenesis, the stained area of CD31 in 10 fields was quantified by using Image Pro Plus. Bars are the mean ± SD (n = 10). The comparisons were made relative to untreated controls, and the different levels of significance was indicated as **P < 0.01. (c) The images were quantified using Image Pro Plus and mean optical densities (of control) of VEGF and HIF-1α were shown. Bars are the mean ± SD (n = 10). The comparisons were made relative to untreated controls, and the different levels of significance was indicated as **P < 0.01.
Mentions: To confirm the macroscopic observations and address the potential effect of GA in vivo, immunohistochemistry was performed. The results showed that the presence of endothelial-specific antibody CD31-stained capillaries in xenografts was dose-dependently reduced by GA treatment (Fig. 6a,b), suggesting GA attenuated the tumor angiogenesis. To investigate whether the anti-angiogenesis effect of GA was due to the decreased level of VEGF and HIF-1α, immunohistochemistry for VEGF and HIF-1α was performed. The same as CD31, the tumor sections treated with GA showed significantly lower levels of VEGF and HIF-1α than that of control tumor tissue (Fig. 6a,c). These results further supported that GA, a HIF-1α inhibitor, is a potential compound for MM therapy.

Bottom Line: Gambogic acid (GA) is the major active ingredient of gamboge, which has been shown to possess antitumor effect by in vitro and in vivo study.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