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.
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.
Affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), Medical School, Zhongda Hospital, Southeast University, Nanjing, China.Show MeSH
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Mentions: Tumor xenografts transplanted by U266 cells were used to evaluate the antitumor effect of GA in BALB/c nude mice in vivo. After 14-day treatments, the tumors were moved and photographed (Fig. 5a). The average tumor size of control group was 615.5 ± 69.8 mm3 while those of GA treated groups were 323.3 ± 53.5 mm3 (2 mg/kg per 2 days) and 163.3 ± 30.1 mm3 (4 mg/kg per 2 days), respectively (Fig. 5b). The average tumor weight of the control group was 0.590 ± 0.099 g, while those of GA treated groups were 0.431 ± 0.074 g (2 mg/kg per 2 days) and 0.223 ± 0.064 g (4 mg/kg per 2 days), respectively (Fig. 5c). The results indicated that GA significantly inhibited tumor growth in a dosage-dependent manner. Moreover, administration of GA did not affect the body weight of mice (Fig. 5d), suggesting the maximal dose of GA (4 mg/kg per 2 days) is not toxic or at least a low toxicity for mice.
Affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), Medical School, Zhongda Hospital, Southeast University, Nanjing, China.