대한임상검사과학회지 (Korean Journal of Clinical Laboratory Science)

  • 제49권2호
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  • Pages.69-78
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  • 2017
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  • 1738-3544(pISSN)
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  • 2288-1662(eISSN)
대한임상검사과학회 (Korean Society for Clinical Laboratory Science)
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게르마늄 농도를 증가 시킨 동충하초 균사체 열수 추출액의 항암효과

Anti-cancer Effect of Hot Water Extract from Mycelium in Germanium-enriched Cordyceps militaris

  • 최정수 (고려대학교 보건과학대학 보건환경융합과학부) ;
  • 허지혜 (동아보건대학교 임상병리과) ;
  • 김대진 (고려대학교 보건과학대학 보건환경융합과학부) ;
  • 남궁수민 (고려대학교 보건과학대학 보건환경융합과학부) ;
  • 이태복 (을지대학교 대학원 시니어헬스케어학과) ;
  • 이민우 (고려대학교 보건과학대학 보건환경융합과학부) ;
  • 김성욱 (고려대학교 보건과학대학 보건환경융합과학부)
  • Choi, Jeong Su (School of Health and Environmental Science, College of Health Sciences, Korea University) ;
  • Heo, Ji Hye (Department of Clinical Laboratory Science, Donga College of Health) ;
  • Kim, Dae Jin (School of Health and Environmental Science, College of Health Sciences, Korea University) ;
  • Namkung, Su Min (School of Health and Environmental Science, College of Health Sciences, Korea University) ;
  • Lee, Tae Bok (Department of Senior Healthcare, Graduate School, Eulji University) ;
  • Lee, Min Woo (School of Health and Environmental Science, College of Health Sciences, Korea University) ;
  • Kim, Suhng Wook (School of Health and Environmental Science, College of Health Sciences, Korea University)
  • 투고 : 2017.03.03
  • 심사 : 2017.05.11
  • 발행 : 2017.06.30
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초록

게르마늄(Ge)은 거의 대부분의 영양분, 동물, 식물에서 발견되는 미량원소로 많은 연구를 통해 항균성 항바이러스성 항종양성 항돌연변이성 및 면역조절 효과를 지닌 것으로 알려져 있다. 또한, 동충하초는 중국의 전통적인 약용 버섯으로 항종양성, 항산화성 및 면역조절 효과 등 다양한 생물학적 활성을 지니고 있으며 미량원소를 축적시키기 효과적인 것으로 알려져 있다. 이런 특성을 이용하여 본 연구는 게르마늄 농도를 증가시킨 동충하초(CMGe)의 열수 추출액을 얻어내고 그 생물학적 특성을 실험하였다. 네 가지 암세포주 Ramos, A549, HepG2, CEM와 MSC에 대한 CMGe의 세포독성을 MTT assay를 통해 확인한 결과, CEM에서 항증식성이 가장 높고 MSC에 대한 세포독성은 낮은 것으로 확인되었다. 마지막으로 누드마우스에 인간 신경아교세포종(U87MG)을 이종이식하여 종양의 부피와 무게를 조사한 결과, CMGe열수 추출액 처리군에서 종양 부피와 무게의 감소를 확인할 수 있었다. 이런 결과는 CMGe가 앞으로 의약 및 제약산업에 다양하게 적용될 수 있을 것으로 기대된다.

Cordyceps militaris has been used in traditional Chinese medicine owing to its anticancer and immunomodulatory activities. Germanium compounds have also been shown to be associated with many pharmacological functions, such as antimicrobial, antiviral, antitumor, antimutagenic, and immunomodulating effects. In this study, we examined the biological properties of hot water extract from mycelial liquid culture of germanium-enriched C. militaris (CMGe). CMGe displayed a concentration-dependent antiproliferation activity against four human cancer cell lines. The antiproliferative activity of CMGe was 2-4-fold lower than that of hot water extract from mycelial liquid culture in C. militaris (CM). However, CM had a concentration-dependent cytotoxicity to human bone marrow-derived mesenchymal stem cells (MSCs). Contrastingly, CMGe did not cause any cellular damage to MSCs. MSCs cultured with CMGe displayed an increased proliferative activity with no cytotoxic effect. The oral administration of CMGe inhibited increased tumor volume and weight compared with the control group. CMGe has the potential to be used as an industrial product in medicinal foods as well as in pharmaceutical products.

키워드

참고문헌

  1. Schroeder HA, Balassa JJ. Abnormal trace metals in man: Germanium. J Chronic Dis. 1967;20(4):211-224. https://doi.org/10.1016/0021-9681(67)90003-3
  2. Schroeder HA, Balassa JJ. Arsenic, germanium, tin, and vanadium in mice: Effects on growth, survival and tissue levels. J Nutr. 1967;92(2):245-252. https://doi.org/10.1093/jn/92.2.245
  3. Sijpesteijn A, Rijkens KF, van der Kerk GJ, Manten A. Antimicrobial activity of organogermanium derivatives. Nature. 1964;201:736.
  4. Aso H, Suzuki F, Ebina T, Ishida N. Antiviral activity of carboxyethylgermanium sesquioxide (Ge-132) in mice infected with influenza virus. J Biol Response Mod. 1989;8(2):180-189.
  5. Brutkiewicz RR, Suzuki F. Biological activities and antitumor mechanism of an immunopotentiating organogermanium compound, Ge-132 (review). In Vivo. 1987;1(4):189-203.
  6. Gerber GB, Leonard A. Mutagenicity, carcinogenicity and teratogenicity of germanium compounds. Mutat Res. 1997;387(3):141-146. https://doi.org/10.1016/S1383-5742(97)00034-3
  7. Jao SW, Lee W, Ho YS. Effect of germanium on 1,2-dimethylhydrazine- induced intestinal cancer in rats. Dis Colon Rectum. 1990;33(2):99-104. https://doi.org/10.1007/BF02055535
  8. Kang KS, Yun JW, Yoon B, Lim YK, Lee YS. Preventive effect of germanium dioxide on the inhibition of gap junctional intercellular communication by TPA. Cancer Lett. 2001;166(2): 147-153. https://doi.org/10.1016/S0304-3835(01)00446-3
  9. Suzuki F, Brutkiewicz RR, Pollard RB. Ability of sera from mice treated with Ge-132, an organic germanium compound, to inhibit experimental murine ascites tumours. Br J Cancer. 1985;52(5):757-763. https://doi.org/10.1038/bjc.1985.254
  10. Han C, Wu G, Yin Y, Shen M. Inhibition by germanium oxide of the mutagenicity of cadmium chloride in various genotoxicity assays. Food Chem Toxicol. 1992;30(6):521-524. https://doi.org/10.1016/0278-6915(92)90104-S
  11. Kada T, Mochizuki H, Miyao K. Antimutagenic effects of germanium oxide on Trp-P-2-induced frameshift mutations in Salmonella typhimurium TA98 and TA1538. Mutat. Res. 1984;125(2):145-151. https://doi.org/10.1016/0027-5107(84)90066-6
  12. Lee CH, Lin RH, Liu SH, Lin-Shiau SY. Effects of germanium oxide and other chemical compounds on phenylmercury acetate-induced genotoxicity in cultured human lymphocytes. Environ Mol Mutagen. 1998;31(2):157-162. https://doi.org/10.1002/(SICI)1098-2280(1998)31:2<157::AID-EM7>3.0.CO;2-J
  13. Aso H, Suzuki F, Yamaguchi T, Hayashi Y, Ebina T, Ishida N. Induction of interferon and activation of NK cells and macrophages in mice by oral administration of Ge-132, an organic germanium compound. Microbiol Immunol. 1985;29(1):65-74. https://doi.org/10.1111/j.1348-0421.1985.tb00803.x
  14. Goodman S. Therapeutic effects of organic germanium. Med Hypotheses. 1988;26(3):207-215. https://doi.org/10.1016/0306-9877(88)90101-6
  15. Ikemoto K, Kobayashi M, Fukumoto T, Morimatsu M, Pollard RB, Suzuki F. 2-Carboxyethylgermanium sesquioxide, a synthetic organogermanium compound, as an inducer of contrasuppressor T cells. Experientia. 1996;52(2):159-166. https://doi.org/10.1007/BF01923363
  16. Nakada Y, Kosaka T, Kuwabara M, Tanaka S, Sato K, Koide F. Effects of 2-carboxythylgerumanium sesquioxide (Ge-132) as an immunological modifier of post-surgical immunosuppression in dogs. J Vet Med Sci. 1993;55(5):795-799. https://doi.org/10.1292/jvms.55.795
  17. Nagata N, Yoneyama T, Yanagida K, Ushio K, Yanagihara S, Matsubara O, et al. Accumulation of germanium in the tissues of a long-term user of germanium preparation died of acute renal failure. J Toxicol Sci. 1985;10(4):333-341. https://doi.org/10.2131/jts.10.333
  18. Obara K, Saito T, Sato H, Yamakage K, Watanabe T, Kakizawa M, et al. Germanium poisoning: clinical symptoms and renal damage caused by long-term intake of germanium. Jpn J Med. 1991;30(1):67-72. https://doi.org/10.2169/internalmedicine1962.30.67
  19. Tao SH, Bolger PM. Hazard assessment of germanium supplements. Regul Toxicol Pharmacol. 1997;25(3):211-219. https://doi.org/10.1006/rtph.1997.1098
  20. Das SK, Masuda M, Sakurai A, Sakakibara M. Medicinal uses of the mushroom Cordyceps militaris: current state and prospects. Fitoterapia. 2010;81(8):961-968. https://doi.org/10.1016/j.fitote.2010.07.010
  21. Gu Y X, Wang ZS, Li SX, Yuan QS. Effects of multiple factors on accumulation of nucleosides and bases in Cordyceps militaris. Food Chem. 2007;102(4):1304-1309. https://doi.org/10.1016/j.foodchem.2006.07.018
  22. Khan MA, Tania M, Zhang D, Chen H. Cordyceps mushroom: a potent anticancer nutraceutical. The Open Nutraceuticals Journal. 2010;3:179-183.
  23. Mao XB, Eksriwong T, Chauvatcharin S, Zhong JJ. Optimization of carbon source/nitrogen ratio for cordycepin production by submerged cultivation of medicinal mushroom Cordyceps militaris. Process Biochem. 2005;40(5):1667-1672. https://doi.org/10.1016/j.procbio.2004.06.046
  24. Won SY, Park EH. Anti-inflammatory and related pharmacological activities of cultured mycelia and fruiting bodies of Cordyceps militaris. J Ethnopharmacol. 2005;96(3):555-561. https://doi.org/10.1016/j.jep.2004.10.009
  25. Dong JZ, Lei C, Ai XR, Wang Y. Selenium enrichment on Cordyceps militaris link and analysis on its main active components. Appl Biochem Biotechnol. 2012;166(5):1215-1224. https://doi.org/10.1007/s12010-011-9506-6
  26. Shang D, Li Y, Wang C, Wang X, Yu Z, Fu X. A novel polysaccharide from Se-enriched Ganoderma lucidum induces apoptosis of human breast cancer cells. Oncol Rep. 2011;25(1):267-272.