Korean Journal of Food Science and Technology (한국식품과학회지)

Korean Society of Food Science and Technology (한국식품과학회)
권호 표지
DOI QR코드

DOI QR Code

Anti-cancer effect of Sarijang on colorectal cancer cells in a xenograft nude mouse model

대장암 세포가 이식된 동물모델에서 사리장의 항암효과에 대한 연구

  • Received : 2018.05.26
  • Accepted : 2018.07.24
  • Published : 2018.08.31
Download PDF
⟨ Previous Next ⟩

Abstract

The current study was conducted to confirm the anti-cancer effect of Sarijang, which is a mixture of extracts from purple bamboo salt, Rhynchosia nulubilis, garlic, and Ulmi cortex. Nude mice were injected with a human-derived colorectal cancer cell (HCT116 cell line) and subsequently administered Sarijang for 4 weeks, following which the body weight, organ weight, and tumor size were measured. To evaluate the anti-cancer mechanism of Sarijang, the levels of p16 and extracellular signal-regulated kinase (ERK), cell cycle regulators in colorectal cancer, were measured. To evaluate the toxicity of Sarijang on liver and kidney, aspartate transaminase, alanine transaminase, blood urea nitrogen, and creatinine were analyzed. Sarijang not only reduced the tumor size by enhancing p16 and suppressing ERK, but also showed no side-effect in the liver and kidneys. Taken together, Sarijang has the potential to inhibit tumor growth without side effects, and may be used as a useful functional food.

본 연구는 사람유래 대장암세포가 이식된 동물모델을 사용하여 사리장의 항암효과를 확인하기 이하여 수행하였다. 사리장은 죽염과 서목태, 마늘과 유근피를 혼합 추출한 물질로써 아이소플라본을 포함하고 있으며 항염, 항산화 등의 효능이 보고된 물질이다. 이러한 사리장을 종양이 이식된 동물모델에 4주간 투여하면서 종양 크기의 변화, 종양 성장인자의 변화와 사리장의 안전성을 평가하였다. 그 결과 사리장은 종양의 크기를 감소시켰으며, 종양 성장과 관련된 ERK와 p16의 발현량을 조절함으로써 종양의 성장을 억제하는 효과를 나타냈다. 또한 사리장을 투여한 시험군에서는 체중, 장기무게, 혈청생화학적검사와 조직학적 검사에서 독성으로 인한 변화가 관찰되지 않았다. 이러한 결과는 사리장이 장기복용이 가능한 항암 보조식품의 소재로써 활용될 수 있다는 것을 의미한다고 할 수 있다.

Keywords

References

  1. Asada T, Ishihara S, Yamane T, Toba A, Yamada A, Oikawa K. Science of bamboo charcoal: study on carbonizing temperature of bamboo charcoal and removal capability of harmful gases. J. Health Sci. 48: 473-479 (2002) https://doi.org/10.1248/jhs.48.473
  2. Chirumbolo S. The role of quercetin, flavonols and flavones in modulating inflammatory cell function. Inflamm. Allergy Drug. Targets 9: 263-285 (2010) https://doi.org/10.2174/187152810793358741
  3. de Leon MP. Familial and Hereditary Tumors. Springer, Switzerland. pp. 35-47 (1994)
  4. Elledge SJ, Richman R, Hall FL, Williams RT, Lodgson N, Harper JW. CDK2 encodes a 33-kDa cyclin A-associated protein kinase and is expressed before CDC2 in the cell cycle. Proc. Natl. Acad. Sci. 89: 2907-2911 (1992) https://doi.org/10.1073/pnas.89.7.2907
  5. Florea AM, Busselberg D. Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers 3: 1351-1371 (2011) https://doi.org/10.3390/cancers3011351
  6. Gorinstein S, Jastrzebski Z, Namiesnik J, Leontowicz H, Leontowicz M, Trakhtenberg S. The atherosclerotic heart disease and protecting properties of garlic: contemporary data. Mol. Nutr. Food Res. 51: 1365-1381 (2007) https://doi.org/10.1002/mnfr.200700064
  7. Hsieh CY, Santell RC, Haslam SZ, Helferich, WG, Estrogenic effects of genistein on the growth of estrogen receptor positive human breast cancer (MCF-7) cells in vitro and in vivo. Cancer Res. 58: 3833-3838 (1998)
  8. Hu C, Zhang Y, Kitts DD. Evaluation of antioxidant and prooxidant activities of bamboo Phyllostachys nigra var. Henonis leaf extract in vitro. J. Agr. Food. Chem. 48: 3170-3176 (2000) https://doi.org/10.1021/jf0001637
  9. Huang JC, Zamble DB, Reardon JT, Lippard SJ, Sancar A. HMG-domain proteins specifically inhibit the repair of the major DNA adduct of the anticancer drug cisplatin by human excision nuclease. Proc. Natl. Acad. Sci. 91: 10394-10398 (1994) https://doi.org/10.1073/pnas.91.22.10394
  10. Ishimi Y. Dietary equol and bone metabolism in postmenopausal Japanese women and osteoporotic mice. J. Nutr. 140: 1373-1376 (2010) https://doi.org/10.3945/jn.110.124842
  11. Kim CJ, Jung YS, Park JH, Kim HJ, Cho YK, Sohn CI, Bang KB. Prevalence, clinicopathologic characteristics, and predictors of interval colorectal cancers in Korean population. Intest. Res. 11: 178-183 (2013) https://doi.org/10.5217/ir.2013.11.3.178
  12. Kim EJ, Jang MK, Yoon EH, Jung CY, Nam DW, Lee SD. Efficacy of pharmacopuncture using root bark of Ulmus davidiana Planch in patients with knee osteoarthritis: a double-blind randomized controlled trial. J. Acupunct. Meridian St. 3: 16-23 (2010) https://doi.org/10.1016/S2005-2901(10)60003-9
  13. Kim HY, Lee ES, Jeong JY, Choi JH, Choi YS, Han DJ. Effect of bamboo salt on the physicochemical properties of meat emulsion systems. Meat Sci. 86: 960-965 (2010) https://doi.org/10.1016/j.meatsci.2010.08.001
  14. Lee MY, Seo CS, Ha H, Jung D, Lee H, Lee NH. Protective effects of Ulmus davidiana var. japonica against OVA-induced murine asthma model via upregulation of heme oxygenase-1. J. Ethnopharmacol. 130: 61-69 (2010) https://doi.org/10.1016/j.jep.2010.04.011
  15. Kim JG, Seo KW, Lee BH, Park MK, Park CW, Shin DW, Hong CM, Han SH, Kim YJ, Cho. 3 months repeated dose toxicity studies of the bamboo salt (Jukyum) in rats. Toxicol. Res. 18: 149-157 (2002)
  16. Klaus SO, Ferrari DM, Wesselborg S, Peter ME. Apoptosis signaling by death receptors. FEBS J. 254: 439-459 (1998)
  17. Koff A, Giordano A, Desai D, Yamashita K, Harper JW, Elledge S. Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle. Science 257: 1689-1694 (1992) https://doi.org/10.1126/science.1388288
  18. Lee Y, Park H, Ryu HS, Chun M, Kang S, Kim HS. Effects of elm bark (Ulmus davidiana var. japonica) extracts on the modulation of immunocompetence in mice. J. Med. Food. 10: 118-125 (2007) https://doi.org/10.1089/jmf.2006.078
  19. Li ZH, Kobayashi M. Plantation future of bamboo in China. J. For. Res.15: 233-242 (2004) https://doi.org/10.1007/BF02911032
  20. Morgan DO. Cyclin-dependent kinases: engines, clocks, and microprocessors. Annu. Rev. Cell. Dev. 13: 261-291 (1997) https://doi.org/10.1146/annurev.cellbio.13.1.261
  21. Nielsen ILF, Williamson G. Review of the factors affecting bioavailability of soy isoflavones in humans. Nutr. Cancer 57: 1-10 (2007) https://doi.org/10.1080/01635580701267677
  22. Nierodzik ML, Karpatkin S. Thrombin induces tumor growth, metastasis, and angiogenesis: Evidence for a thrombin-regulated dormant tumor phenotype. Cancer Cell 10; 355-362 (2006) https://doi.org/10.1016/j.ccr.2006.10.002
  23. Park HY, Choi YH, Choi EA. Anti-inflammatory effects of sarijang in lipopolysaccharide-activated BV2 microglial cells. Cancer Prev. Res. 16: 348-357 (2011)
  24. Pil PM, Lippard SJ. Specific binding of chromosomal protein HMG1 to DNA damaged by the anticancer drug cisplatin. Science 256: 234-237 (1992) https://doi.org/10.1126/science.1566071
  25. Resch K, Ernst E. Garlic (Allium sativum) a potent medicinal plant. Fortschr. Med. 113: 311-315 (1995)
  26. Rietjens IM, Sotoca AM, Vervoort J, Louisse J. Mechanisms underlying the dualistic mode of action of major soy isoflavones in relation to cell proliferation and cancer risks. Mol. Nutr. Food Res. 57: 100-113 (2013) https://doi.org/10.1002/mnfr.201200439
  27. Shin HY, Lee EH, Kim CY, Shin TY, Kim SD, Song YS. Antiinflammatory activity of Korean folk medicine purple bamboo salt. Immunopharmacol. Immunotoxicol. 25: 377-384 (2003) https://doi.org/10.1081/IPH-120024505
  28. Shin HY, Na HJ, Moon PD, Shin T, Shin TY, Kim SH. Inhibition of mast cell-dependent immediate-type hypersensitivity reactions by purple bamboo salt. J. Ethnopharmacol. 91: 153-157 (2004) https://doi.org/10.1016/j.jep.2003.12.006
  29. Taylor CK, Levy RM, Elliott JC, Burnett BP. The effect of genistein aglycon on cancer and cancer risk: a review of in vitro, preclinical, and clinical studies. Nutr. Rev. 67: 398-415 (2009) https://doi.org/10.1111/j.1753-4887.2009.00213.x
  30. Vermeulen K, Van Bockstaele DR, Berneman ZN. The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 36: 131-149 (2003) https://doi.org/10.1046/j.1365-2184.2003.00266.x
  31. Zhao X, Deng X, Park KY, Qiu L, Pang L. Purple bamboo salt has anticancer activity in TCA8113 cells in vitro and preventive effects on buccal mucosa cancer in mice in vivo. Exp. Ther. Med. 5: 549-554 (2013) https://doi.org/10.3892/etm.2012.848
  32. Zhao X, Kim SY, Park KY. Bamboo salt has in vitro anticancer activity in HCT-116 cells and exerts anti-metastatic effects in vivo. J. Med. Food 16: 9-19 (2013) https://doi.org/10.1089/jmf.2012.2316