YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
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Therapeutic Effect of 18β-Glycyrrhetinic Acid on HT-29 Cancer Cell in a Murine Xenograft Model

HT-29 암세포 이종이식으로 유발된 종양에 대한18β-Glycyrrhetinic Acid의 치료효과

  • Han, Yongmoon (Department of Immuno Microbiology, College of Pharmacy/Dongduk Women's University) ;
  • Kim, Jeonghyeon (Department of Immuno Microbiology, College of Pharmacy/Dongduk Women's University)
  • 한용문 (동덕여자대학교 약학대학 면역.미생물학교실) ;
  • 김정현 (동덕여자대학교 약학대학 면역.미생물학교실)
  • Received : 2015.05.28
  • Accepted : 2015.06.18
  • Published : 2015.08.30
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Abstract

In the present study, we determined the effect of $18{\beta}$-glycyrrhetinic acid ($18{\beta}$-GA) in the mice model bearing xenografts of HT-29 human colon cancer cell line. Data from the cytotoxicity assay displayed that $18{\beta}$-GA induced cell death in HT-29. The cytotoxicity was enhanced as the $18{\beta}$-GA treatment was prolonged. In case of 72 hrs treatment, $LD_{50}$ of $18{\beta}$-GA was approximately $90{\mu}M$, and the efficacy at $100{\mu}M$ of $18{\beta}$-GA appeared to be equivalent to that of doxorubicin at $1{\mu}M$. Based on the in vitro data, we tested the anti-tumor effect of $18{\beta}$-GA in thymic mice (Balb/c strain). Xenograft tumors were generated by subcutaneous injection of HT-29 ($3{\times}10^6cells/mouse$) to mice and the mice were treated intraperitoneally with $18{\beta}$-GA ($50{\mu}g/time/mouse$) every other day for 4 times. The tumor volumes were measured for a period of 14 days. Data displayed that the $18{\beta}$-GA treatment reduced the tumor volumes (P < 0.05) as compared to control mice. However, this activity was demolished when athymic mice (Balb/c nu/nu) were used instead of thymic mice. This observation appeared that T lymphocyte played an important role in the anti-tumor activity. In conclusion, our results indicate that $18{\beta}$-GA has anti-tumor activity in HT-29 tumor-bearing mice, which may be associated with T cells.

Keywords

References

  1. Teelucksingh, S., Mackie, A. D., Burt, D., McIntyre, M. A., Brett, L. and Edwards, C. R. : Potentiation of hydrocortisone activity in skin by glycyrrhetinic acid. Lancet 335, 1060 (1990). https://doi.org/10.1016/0140-6736(90)92633-S
  2. Marandici, A. and Monder, C. : Inhibition by glycyrrhetinic acid of rat tissue 11-hydroxysteroid dehydrogenase in vivo. Steroids 58, 153 (1993). https://doi.org/10.1016/0039-128X(93)90062-R
  3. Gumpricht, E., Dahl, R., Devereaux, M. W. and Sokol, R. J. : Licorice compounds glycyrrhizin and $18{\beta}$-glycyrrhetinic acid are potent modulators of bile acid-induced cytotoxicity in rat hepatocytes. J. Biol. Chem. 280, 10556 (2005). https://doi.org/10.1074/jbc.M411673200
  4. Han, Y. : $18{\beta}$-Glycyrrhetinic acid induces protective anti-Candida albicans antibody by its immunoadjuvant activity. Yakhak Hoeji 52, 494 (2008).
  5. Kim, J., Joo, I., Kim, H. and Han, Y. : $18{\beta}$-Glycyrrhetinic acid induces immunological adjuvant activity of Th1 against Candida albicans surface mannan. Phytomedicine 20, 951 (2013). https://doi.org/10.1016/j.phymed.2013.04.008
  6. Han, Y. : Effect of $18{\beta}$-glycyrrhetinic acid on septic arthritis caused by Candida albicans. Yakhak Hoeji 51, 476 (2007).
  7. Han, Y. and Rhew, K. Y. : Ginsenoside Rd induces protective anti-Candida albicans antibody through immunological adjuvant activity. : Int. Immunopharmacol. 17, 651 (2013). https://doi.org/10.1016/j.intimp.2013.08.003
  8. Takashi, N., Minoru, N., Marimo, S., Kenji, I., Hidemitsu, K., Masashi, S., Akio, O., Toshiaki, K. and Shinichiro, N. : The critical role of Th1-dominant immunity in tumor immunology. Cancer Chemother. Pharmacol. 46, S52 (2000). https://doi.org/10.1007/PL00014051
  9. Baier, P. K., Wolff-Vorbeck, G., Eggstein, S., Baumgartner, U. and Hopt, U. T. : Cytokine expression in colon carcinoma. Anticancer Res. 25, 2135 (2005).
  10. Abe, H., Ohya, N., Yamamoto, K. F., Shibuya, T., Arichi, S. and Odashimag, S. : Effect of glycyrrhizin and glycyrrhetinic acid on growth and melanogenesis in cultured B16 melanoma cells. Eur. J. Cancer Clin. On. 23, 1541 (1987). https://doi.org/10.1016/0277-5379(87)90098-8
  11. Agarwal, M. K., Iqbal, M. A. and Athar, M. : Inhibitory effect of $18{\beta}$-glycyrrhetinic acid on 12-O-tetradecanoyl phorbol-13-acetate-induced cutaneous oxidative stress and tumor promotion in mice. Redox Report 10, 151 (2005). https://doi.org/10.1179/135100005X57346
  12. Inoue, H., Mori, T., Shibata, S. and Koshihara, Y. : Modulation by glycyrrhetinic acid derivatives of TPA-induced mouse ear oedema. Br. J. Pharmacol. 96, 204 (1989). https://doi.org/10.1111/j.1476-5381.1989.tb11801.x
  13. Makino, T., Tsubouchi, R., Murakami, K., Haneda, M. and Yoshino, M. : Generation of reactive oxygen species and induction of apoptosis of HL60 cells by ingredients of traditional herbal medicine, Sho-saiko-to. Basic Clin. Pharmacol. Toxicol. 98, 401 (2006). https://doi.org/10.1111/j.1742-7843.2006.pto_328.x
  14. Kamran, G., Weining, Z., Monika, F. S., Thomas, S. and Hiremagalur, N. J. : Studies on the antitumor activity and biochemical actions of cyclopentenyl cytosine against human colon carcinoma HT-29 in vitro and in vivo. Life Science 64, 103 (1998). https://doi.org/10.1016/S0024-3205(98)00540-2
  15. Nishikawa, T., Ramesh, R., Munshi, A., Chada, S. and Meyn, R. E. : Adenovirus-mediated mda-7 (IL24) gene therapy suppresses angiogenesis and sensitizes NSCLC xenograft tumors to radiation. Mol. Ther. 9, 818 (2004). https://doi.org/10.1016/j.ymthe.2004.03.014
  16. Aparicio, S., Hidalgo, M. and Kung, A. L. : Examining the utility of patient-derived xenograft mouse models. Nat. Rev. Cancer 15, 311 (2015). https://doi.org/10.1038/nrc3944
  17. Kim, H., Kim, S., Lee, J. H. and Han, Y. : Antiumor effect of $18{\beta}$-glycyrrhetinic acid against human tumor xenografts caused by A549 cancer cell. Yakhak Hoeji 55, 39 (2011).
  18. Jung, K. W., Won, Y. J., Kong, H. J., Oh, C. M., Cho, H., Lee, D. H. and Lee, K. H. : Cancer statistics in Korea: Incidence, Mortality, Sutvival, and Prevalence in 2012. Cancer Res. Treat. 47, 127 (2015). https://doi.org/10.4143/crt.2015.060
  19. Siegel, R. L. Miller, K. D. and Jemal, A. : Cancer Statistics, 2015. CA Cancer J. Clin. 65, 5 (2015). https://doi.org/10.3322/caac.21254
  20. Manning, D. D., Reed, N. D. and Shaffer, C. F. : Maintenance of skin xenografts of widely divergent phylogenetic origin of congenitally athymic (nude) mice. J. Exp. Med. 38, 488 (1973).
  21. Price, J. E. : Spontaneous and experimental metastasis models: nude mice. Methods Mol. Biol. 1070, 223 (2014). https://doi.org/10.1007/978-1-4614-8244-4_17
  22. Lee, J. Y., Lee, J. H., Park, J. H., Kim, S. Y., Choi, J. Y., Lee, S. H., Kim, Y. S., Kang, S. S., Jang, E. C. and Han, Y. : Liquiritigenin, a licorice flavonoid, helps mice resist disseminatedcandidiasis due to Candida albicans by Th1 immune response, whereas liquiritin, its glycoside form, does not. Int. Immunopharm. 9, 632 (2009). https://doi.org/10.1016/j.intimp.2009.02.007
  23. Lee, J. H., Park, J. H., Kim, Y. S. and Han, Y. : Chlorogenic acid, a polyphenolic compound, treats mice with septic arthritis caused by Candida albicans. Int. Immunopharmacol. 10, 1681 (2008).
  24. Sirotnak, F. M., Zakowski, M. F., Miller, V. A., Scher, H. I. and Kris, M. G. : Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase. Clin. Cancer Res. 6, 4885 (2000).
  25. Ma, Y., Trump, D. L. and Johnson, C. S. : Vitamin D in combination cancer treatment. J. Cancer. 15, 101 (2010).