18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes

  • Authors:
    • Aditya V. Shetty
    • Sivasakthivel Thirugnanam
    • Gajalakshmi Dakshinamoorthy
    • Abhilash Samykutty
    • Guoxing Zheng
    • Aoshuang Chen
    • Maarten C. Bosland
    • André Kajdacsy-Balla
    • Munirathinam Gnanasekar
  • View Affiliations

  • Published online on: May 31, 2011     https://doi.org/10.3892/ijo.2011.1061
  • Pages:635-640
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Abstract

Glycyrrhetinic acid is an active triterpenoid metabolite of glycyrrhizin abundantly present in licorice roots. Glycyrrhetinic acid exists as α and β stereo-isomeric forms. Both stereo-isomeric forms are known to have anti-inflammatory and anticancer activity. However, the effects and anticancer mechanism of α glycyrrhetinic acid in prostate cancer cells has not yet been evaluated. Therefore, we investigated the growth inhibition, induction of apoptosis and the anticancer mechanisms of 18α-glycyrrhetinic acid (AGA), on the androgen-independent metastatic prostate cancer cell line DU-145. Our results showed that AGA inhibited proliferation and growth of these cells by inducing apoptosis as determined by Annexin V and flow cytometry analyses. Our studies also showed that HUVEC tube formation was drastically reduced when cultured in conditioned medium of AGA-treated DU-145 cells. In addition, AGA treatment prevented the invasion of DU-145 prostate cancer cells on matrigel coated transwells via down-regulation of NF-κB (p65), VEGF and MMP-9 expression. Furthermore, AGA treatment also down-regulated the expression of pro-inflammatory cytokine/growth factor genes HMGB1, IL-6 and IL-8 in DU-145 cells. Interestingly, AGA simultaneously upregulated the expression of non-steroidal anti-inflammatory gene-1 (NAG-1) in DU-145 cells suggesting its anti-inflammatory activity on prostate cancer cells. Taken together, the results of this study suggest that AGA may be a promising anticancer agent that merits further investigation for the chemoprevention and treatment of prostate cancer.

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September 2011
Volume 39 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Shetty, A.V., Thirugnanam, S., Dakshinamoorthy, G., Samykutty, A., Zheng, G., Chen, A. ... Gnanasekar, M. (2011). 18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes. International Journal of Oncology, 39, 635-640. https://doi.org/10.3892/ijo.2011.1061
MLA
Shetty, A. V., Thirugnanam, S., Dakshinamoorthy, G., Samykutty, A., Zheng, G., Chen, A., Bosland, M. C., Kajdacsy-Balla, A., Gnanasekar, M."18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes". International Journal of Oncology 39.3 (2011): 635-640.
Chicago
Shetty, A. V., Thirugnanam, S., Dakshinamoorthy, G., Samykutty, A., Zheng, G., Chen, A., Bosland, M. C., Kajdacsy-Balla, A., Gnanasekar, M."18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes". International Journal of Oncology 39, no. 3 (2011): 635-640. https://doi.org/10.3892/ijo.2011.1061