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Antitumor and antimetastatic effects of licochalcone A in mouse models

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Abstract

Licochalcone A (LicA), a major phenolic constituent of licorice, has antiproliferative and anti-inflammatory properties in human and murine cell lines. We previously showed that LicA down-regulates the expression of cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) via the modulation of nuclear factor-κB and activator protein-1 activation in cell culture. We therefore tested whether LicA inhibits carcinogenesis and metastasis in mouse models. To induce colon carcinogenesis, C57BL/6 mice were given a single intraperitoneal injection of azoxymethane (10 mg/kg body weight), followed by 1% dextran sulfate sodium in the drinking water. Additionally, we also assessed the effect of LicA on liver metastasis by intrasplenic injection of BALB/c mice with CT-26 cells. Feeding the mice with LicA (5, 15, and 30 mg/kg body weight) significantly reduced tumor formation as well as the number of cells expressing proliferating cell nuclear antigen, β-catenin, COX-2, and iNOS in the colon. LicA also decreased colon levels of proinflammatory cytokines and chemokines. In addition, LicA significantly increases survival of animals and inhibited liver metastasis as well as the expression of matrix metalloproteinase-9 in the liver. These preclinical studies indicate that LicA has potent antitumor and antimetastatic activity, suggesting that LicA could increase efficacy and improve patient outcomes in colorectal cancer.

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Acknowledgment

This work was supported by a Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean government (MOST; R01-2007-000-20164).

Conflict of interest statement

The authors declare that they have no conflict of interests.

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Authors and Affiliations

  1. Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University, Chuncheon, South Korea

    Jin-Kyung Kim, Eun Kyung Shin, Jun Hong Park & Yoon Hee Kim

  2. Department of Food Science and Nutrition, Hallym University, Chuncheon, 200-702, South Korea

    Jung Han Yoon Park

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  1. Jin-Kyung Kim
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Correspondence to Jin-Kyung Kim or Jung Han Yoon Park.

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Supplementary Figure 1

Microscopic view of the colon on day 56 after AOM injection. Representative microscopic pictures of the H&E staining showing the effect of LicA on tumorigeneis. Arrow indicates infilteration of inflammatory cells. Original magnification, ×40 (upper panel), ×200 (middle panel), and ×400 (lower panel). (PDF 217 kb)

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Kim, JK., Shin, E.K., Park, J.H. et al. Antitumor and antimetastatic effects of licochalcone A in mouse models. J Mol Med 88, 829–838 (2010). https://doi.org/10.1007/s00109-010-0625-2

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  • DOI: https://doi.org/10.1007/s00109-010-0625-2

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