Toxicological Studies of Gambogic Acid and its Potential Targets in Experimental Animals

Guo, Qinglong; Qi, Qi; You, Qidong; Gu, Hong-Yan; Zhao, Li; Wu, Zhao-Qiu

doi:10.1111/j.1742-7843.2006.pto_485.x

Cited by 54 publications

(41 citation statements)

References 17 publications

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“…Several studies also confirmed that GA was equally effective at suppressing the growth of transplanted tumors in animal models (15)(16)(17). Moreover, it was also reported that gA exhibits low toxicity against normal tissues (18,19).…”

Section: Introductionmentioning

confidence: 58%

Gambogic acid inhibits the growth of osteosarcoma cells in vitro by inducing apoptosis and cell cycle arrest

Zhao

Zhou²,

Zhang³

et al. 2011

Oncol Rep

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Abstract. the natural product gambogic acid (gA) has been demonstrated to be a promising chemotherapeutic drug for some cancers because of its ability to induce apoptosis and cell cycle arrest. Until now, no studies have looked at the role of gA in osteosarcoma. In this study, we observed the effects of gA on the growth and apoptosis of osteosarcoma cells in vitro. We found that gA treatment inhibits the proliferation of osteosarcoma cells by inducing cell cycle arrest. Moreover, we found that gA induces apoptosis in Mg63, Hos and U2os cells. Furthermore, we showed that gA treatment elevates the Bax/Bcl-2 ratio. gA mediated the g0/g1 phase arrest in U2os cells; this arrest was associated with a decrease in phospho-gsK3-ß (ser9) and the expression of cyclin D1. similarly, in Mg63 cells, gA mediated g2/M cell cycle arrest, which was associated with a decrease in phospho-cdc2 (Thr 161) and cdc25B. Overall, our findings suggest that gA may be an effective anti-osteosarcoma drug because of its capability to inhibit proliferation and induce apoptosis of osteosarcoma cells.

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Section: Introductionmentioning

confidence: 58%

Gambogic acid inhibits the growth of osteosarcoma cells in vitro by inducing apoptosis and cell cycle arrest

Zhao

Zhou²,

Zhang³

et al. 2011

Oncol Rep

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“…The in vivo activity of GA and its therapeutic index has been explored previously in rodents (2,6). Using a prostate cancer xenograft model, for example, it was recently reported that GA effectively inhibited tumor angiogenesis and suppressed tumor growth with few side effects, where GA was delivered by s.c. injection daily for 15 days (4).…”

Section: Discussionmentioning

confidence: 99%

“…This natural product also displays antitumor activity in preclinical mouse models involving human tumor xenografts (3 -5). In contrast, GA is reportedly well tolerated in mice and rats (2,4,6), suggesting that a therapeutic window might be identified at which tumor but not normal cells are killed. It would therefore be interesting to know the cytotoxic mechanism of GA.…”

Section: Introductionmentioning

confidence: 97%

Gambogic acid is an antagonist of antiapoptotic Bcl-2 family proteins

Zhai

Jin

Shiau

et al. 2008

Molecular Cancer Therapeutics

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The natural product gambogic acid (GA) has been reported to have cytotoxic activity against tumor cells in culture and was identified as an active compound in a cell-based highthroughput screening assay for activators of caspases, proteases involved in apoptosis. Using the antiapoptotic Bcl-2 family protein, Bfl-1, as a target for screening of a library of natural products, we identified GA as a competitive inhibitor that displaced BH3 peptides from Bfl-1 in a fluorescence polarization assay. Analysis of competition for BH3 peptide binding revealed that GA inhibits all six human Bcl-2 family proteins to various extents, with Mcl-1 and Bcl-B the most potently inhibited [concentrations required for 50% inhibition (IC 50 ), <1Mmol/L]. Competition for BH3 peptide binding was also confirmed using a timeresolved fluorescence resonance energy transfer assay.

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“…In the meantime, the weight of the heart, liver, spleen, lung, kidney, and brain were measured and recorded. The organ-body index was calculated according to the following formula: 19 Organ-body weight index (%) = Wet organ weight/Body weight × 100% (3)…”

Section: Blood Analysismentioning

confidence: 99%

Biocompatibility of Fe3O4@Au composite magnetic nanoparticles in vitro and in vivo

Li¹,

Liu²,

Zhong³

et al. 2011

IJN

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Purpose: This research was conducted to assess the biocompatibility of the core-shell Fe 3 O 4 @ Au composite magnetic nanoparticles (MNPs), which have potential application in tumor hyperthermia. Methods: Fe 3 O 4 @Au composite MNPs with core-shell structure were synthesized by reduction of Au 3+ in the presence of Fe 3 O 4 -MNPs prepared by improved co-precipitation. Cytotoxicity assay, hemolysis test, micronucleus (MN) assay, and detection of acute toxicity in mice and beagle dogs were then carried out. Results:The result of cytotoxicity assay showed that the toxicity grade of this material on mouse fibroblast cell line (L-929) was classified as grade 1, which belongs to no cytotoxicity. Hemolysis rates showed 0.278%, 0.232%, and 0.197%, far less than 5%, after treatment with different concentrations of Fe 3 O 4 @Au composite MNPs. In the MN assay, there was no significant difference in MN formation rates between the experimental groups and negative control (P . 0.05), but there was a significant difference between the experimental groups and the positive control (P , 0.05). The median lethal dose of the Fe 3 O 4 @Au composite MNPs after intraperitoneal administration in mice was 8.39 g/kg, and the 95% confidence interval was 6.58-10.72 g/kg, suggesting that these nanoparticles have a wide safety margin. Acute toxicity testing in beagle dogs also showed no significant difference in body weight between the treatment groups at 1, 2, 3, and 4 weeks after liver injection and no behavioral changes. Furthermore, blood parameters, autopsy, and histopathological studies in the experimental group showed no significant difference compared with the control group. Conclusion:The results indicate that Fe 3 O 4 @Au composite MNPs appear to be highly biocompatible and safe nanoparticles that are suitable for further application in tumor hyperthermia.

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Toxicological Studies of Gambogic Acid and its Potential Targets in Experimental Animals

Cited by 54 publications

References 17 publications

Gambogic acid inhibits the growth of osteosarcoma cells in vitro by inducing apoptosis and cell cycle arrest

Gambogic acid inhibits the growth of osteosarcoma cells in vitro by inducing apoptosis and cell cycle arrest

Gambogic acid is an antagonist of antiapoptotic Bcl-2 family proteins

Biocompatibility of Fe3O4@Au composite magnetic nanoparticles in vitro and in vivo

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