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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 cytotoxicity against myeloma U266 cells. (a) The chemical structure of GA. (b) U266 cells were treated with various concentrations of GA for 8 h under normoxia and hypoxia condition. Cell viability was detected by CCK8 assay. Bars are the mean ± SD (n = 3).
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fig01: Effect of gambogic acid (GA) on the cytotoxicity against myeloma U266 cells. (a) The chemical structure of GA. (b) U266 cells were treated with various concentrations of GA for 8 h under normoxia and hypoxia condition. Cell viability was detected by CCK8 assay. Bars are the mean ± SD (n = 3).

Mentions: Gambogic acid (GA), a main active ingredient of gamboge, is a brownish to orange dry resin secreted from Garcinia hanburyi, which is a plant distributed widely in nature (Fig. 1). Recently, in vitro and in vivo studies have demonstrated that GA exerts potent anti-tumor effects on solid tumors and hematological malignancies.(19) In addition, GA can inhibit angiogenesis through suppressing secretion of VEGF.(20)


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 cytotoxicity against myeloma U266 cells. (a) The chemical structure of GA. (b) U266 cells were treated with various concentrations of GA for 8 h under normoxia and hypoxia condition. Cell viability was detected by CCK8 assay. Bars are the mean ± SD (n = 3).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317858&req=5

fig01: Effect of gambogic acid (GA) on the cytotoxicity against myeloma U266 cells. (a) The chemical structure of GA. (b) U266 cells were treated with various concentrations of GA for 8 h under normoxia and hypoxia condition. Cell viability was detected by CCK8 assay. Bars are the mean ± SD (n = 3).
Mentions: Gambogic acid (GA), a main active ingredient of gamboge, is a brownish to orange dry resin secreted from Garcinia hanburyi, which is a plant distributed widely in nature (Fig. 1). Recently, in vitro and in vivo studies have demonstrated that GA exerts potent anti-tumor effects on solid tumors and hematological malignancies.(19) In addition, GA can inhibit angiogenesis through suppressing secretion of VEGF.(20)

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