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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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Gambogic acid (GA) inhibited tumor growth in a xenograft mouse model. The BALB/c nude mice were injected with U266 cells for some days followed by treatment with solvent or various doses of GA for 14 days. Then, the mice were killed, tumor removed and photographed (a). In addition, the tumor size (b), weight (c) and body weight (d) were measured. Bars are shown as mean ± SD (n = 6). The comparisons were made relative to untreated controls, and the different levels of significance were indicated as *P < 0.05 and **P < 0.01.
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fig05: Gambogic acid (GA) inhibited tumor growth in a xenograft mouse model. The BALB/c nude mice were injected with U266 cells for some days followed by treatment with solvent or various doses of GA for 14 days. Then, the mice were killed, tumor removed and photographed (a). In addition, the tumor size (b), weight (c) and body weight (d) were measured. Bars are shown as mean ± SD (n = 6). The comparisons were made relative to untreated controls, and the different levels of significance were indicated as *P < 0.05 and **P < 0.01.

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.


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 growth in a xenograft mouse model. The BALB/c nude mice were injected with U266 cells for some days followed by treatment with solvent or various doses of GA for 14 days. Then, the mice were killed, tumor removed and photographed (a). In addition, the tumor size (b), weight (c) and body weight (d) were measured. Bars are shown as mean ± SD (n = 6). The comparisons were made relative to untreated controls, and the different levels of significance were indicated as *P < 0.05 and **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig05: Gambogic acid (GA) inhibited tumor growth in a xenograft mouse model. The BALB/c nude mice were injected with U266 cells for some days followed by treatment with solvent or various doses of GA for 14 days. Then, the mice were killed, tumor removed and photographed (a). In addition, the tumor size (b), weight (c) and body weight (d) were measured. Bars are shown as mean ± SD (n = 6). The comparisons were made relative to untreated controls, and the different levels of significance were indicated as *P < 0.05 and **P < 0.01.
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.

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