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Involvement of matrix metalloproteinase 2 and 9 in gambogic acid induced suppression of MDA-MB-435 human breast carcinoma cell lung metastasis

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Abstract

Cancer cell invasion is one of the crucial events in local spreading, growth, and metastasis of tumors. The present study investigated the antiinvasive and antimetastatic action of gambogic acid (GA) in MDA-MB-435 human breast carcinoma cells. GA caused a concentration-dependent suppression of cell invasion through Matrigel and significantly inhibited lung metastases of the cells transplanted in vivo. The potent effects of GA have been attributed to its ability to reduce the expression of matrix metalloproteinases (MMP) 2 and 9 in vitro and in vivo both at the protein and mRNA levels, which were associated with protein kinase C (PKC) signaling pathway as supported by the diminished antiinvasive effect of GA in the presence of specific activator of the pathway. Collectively, our data demonstrated that GA exhibited antiinvasion properties on highly invasive cancer cells via PKC mediated MMP-2/9 expression inhibition. This indicated that GA can be served as a potential novel therapeutic candidate for the treatment of cancer metastasis.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 30472044, 30701032, and 90713038) and a startup fund from Florida International University.

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Authors and Affiliations

  1. Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, Jiangsu, 210009, People’s Republic of China

    Qi Qi, Hongyan Gu, Yong Yang, Na Lu, Jie Zhao, Wei Liu, Qi-dong You & Qinglong Guo

  2. Department of Chemistry and Biochemistry, Florida International University, 11200 SW 8th St., Miami, FL, 33199, USA

    Hua Ling & Xiaotang Wang

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  1. Qi Qi
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Correspondence to Qi-dong You, Xiaotang Wang or Qinglong Guo.

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Figure S1

Effect of GA on the tumor growth and tumor lung metastasis in mice bearing MDA-MB-435 human breast carcinoma cell. A. effects of GA on the tumor weight of the nude mice bearing MDA-MB-435 cells. B, the percentage of the mice occurred lung metastasis. C. quantitative evaluation of detectable lung metastases; Data represent the means ± SEM from three independent experiments. *p < 0.05, **p < 0.01 vs. NS group. (DOC 21.3 KB)

Table S1

The sequences of PCR primers. (DOC 26.0 KB)

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Qi, Q., Gu, H., Yang, Y. et al. Involvement of matrix metalloproteinase 2 and 9 in gambogic acid induced suppression of MDA-MB-435 human breast carcinoma cell lung metastasis. J Mol Med 86, 1367–1377 (2008). https://doi.org/10.1007/s00109-008-0398-z

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