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Antitumor and antiangiogenic effects of GA-13315, a gibberellin derivative

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Summary

This study showed that 13-chlorine-3,15-dioxy-gibberellic acid methyl ester (GA-13315), a gibberellin derivative, possessed high antitumor and antiangiogenic activity in vitro and in vivo. Cytotoxicity assays showed that GA-13315 was a potential and efficient antitumor compound, with inhibitory concentration 50 (IC50) values ranging from 0.13 to 30.28 μg/ml in 12 human tumor cell lines, and it showed moderate toxicity to peripheral blood mononuclear cells with an IC50 value of 14.2 μg/ml. Administration of 0.5 or 2.5 mg/kg GA-13315 for 23 days significantly inhibited tumor growth of human non-small cell lung tumor (A549) xenografts, with relative growth rates ranging from 29.91% to 35.05%. Acute toxicity was determined in ICR mice, and the lethal dose 50 (LD50) was 4.19 g/kg after intragastric administration. The high antitumor potency of GA-13315 occurred in parallel with its antiangiogenic activity. In vitro, GA-13315 inhibited recombinant human epithelial growth factor-induced chemotactic motility and capillary-like tube formation of primary cultured human endothelial cells. Furthermore, GA-13315 decreased the factor VIII+ microvessel density and vascular endothelial growth factor expression in A549 tumors, indicating its antiangiogenic efficacy in vivo. These results indicate that the antiangiogenic activity of GA-13315 contributes to its anticancer properties. Further studies are needed to investigate the use of GA-13315 as an anticancer drug.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 20925205 to H. Zhang, No. 30660213 to C. Qing), and a grant from the Natural Science Foundation of Yunnan Province , China (No. 2007C008Z to C. Qing).

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Authors and Affiliations

  1. Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, 650031, People’s Republic of China

    Yanli Zhang, Hui Zhang, Haixia Zhao & Chen Qing

  2. Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming, Yunnan, 650091, People’s Republic of China

    Jingbo Chen, Xianghui Zeng & Hongbin Zhang

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  1. Yanli Zhang
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  2. Hui Zhang
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  3. Jingbo Chen
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  4. Haixia Zhao
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  5. Xianghui Zeng
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  6. Hongbin Zhang
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  7. Chen Qing
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Correspondence to Hongbin Zhang or Chen Qing.

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Zhang, Y., Zhang, H., Chen, J. et al. Antitumor and antiangiogenic effects of GA-13315, a gibberellin derivative. Invest New Drugs 30, 8–16 (2012). https://doi.org/10.1007/s10637-010-9501-8

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  • DOI: https://doi.org/10.1007/s10637-010-9501-8

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