Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
권호 표지
DOI QR코드

DOI QR Code

Anticancer activity of subfractions containing pure compounds of Chaga mushroom (Inonotus obliquus) extract in human cancer cells and in Balbc/c mice bearing Sarcoma-180 cells

  • Chung, Mi-Ja (Department of Food Science and Biotechnology, School of Biotechnology and Bioengineering, Kangwon National University) ;
  • Chung, Cha-Kwon (Department of Food and Nutrition, Hallym University) ;
  • Jeong, Yoon-Hwa (Department Food Science and Nutrition, Dankook University) ;
  • Ham, Seung-Shi (Department of Food Science and Biotechnology, School of Biotechnology and Bioengineering, Kangwon National University)
  • Received : 2010.02.23
  • Accepted : 2010.05.24
  • Published : 2010.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

The Chaga mushroom (Inonotus obliquus) has been used in folk medicine to treat cancers. However, limited information exists on the underlying anticancer effects of the major component of I. obliquus in vivo. We hypothesize that the pure compounds ($3{\beta}$-hydroxy-lanosta-8,24-dien-21-al, inotodiol and lanosterol, respectively) separated from I. obliquus would inhibit tumor growth in Balbc/c mice bearing Sarcoma-180 cells (S-180) in vivo and growth of human carcinoma cells in vitro. To test this hypothesis, the growth inhibition of each subfraction isolated from I. obliquus on human carcinoma cell lines (lung carcinoma A-549 cells, stomach adenocarcinoma AGS cells, breast adenocarcinoma MCF-7 cells, and cervical adenocarcinoma HeLa cells) was tested in vitro. Then, after S-180 implantation, the mice were fed a normal chow supplemented with 0, 0.1 or 0.2 mg of subfraction 1, 2 or 3 per mouse per day. All of the subfractions isolated from I. obliquus showed significant cytotoxic activity against the selected cancer cell lines in vitro. Subfraction 1 was more active than subfraction 2 and subfraction 3 against the A549, AGS and MCF-7 cancer cell lines in vitro. In in vivo results, subfraction 1 isolated from I. obliquus at concentrations of 0.1 and 0.2 mg/mouse per day significantly decreased tumor volume by 23.96% and 33.71%, respectively, as compared with the control. Subfractions 2 and 3 also significantly inhibited tumor growth in mice bearing S-180 as compared with the control mouse tumor. Subfraction 1 isolated from I. obliquus showed greater inhibition of tumor growth than subfractions 2 and 3, which agrees well with the in vitro results. The results suggest that I. obliquus and its compounds in these subfractions isolated from I. obliquus could be used as natural anticancer ingredients in the food and/or pharmaceutical industry.

Keywords

References

  1. Sporn MB. Prevention of cancer in the next millennium: report of the chemoprevention working group to the American association for cancer research. Cancer res 1999;59:4743-58.
  2. Roland JF, Chmielewicz ZF, Weiner BA, Gross AM, Boening OP, Luck JV, Bardos TJ, Reilly HC, Sugiura K, Stock CC, Lucas EH, Byerrum RU, Scevena JA. Calvacin: A new antitumor agent. Science 1960;132:1897. https://doi.org/10.1126/science.132.3443.1897
  3. Gregory FJ, Healy EM, Agersborg HP Jr, Warren GH. Studies on antitumor substances produced by Basidiomycetes. Mycologia 1966;58:80-90. https://doi.org/10.2307/3756990
  4. Saar M. Fungi in Khanty folk medicine. J Ethnopharmacol 1991;31:175-9. https://doi.org/10.1016/0378-8741(91)90003-V
  5. Ham SS, Oh SW, Kim YK, Shin KS, Chang HY, Chung GH. Antimutagenic and cytotoxic effects of ethanol extract from the Inonotus obliquus. Journal of the Korean Society of Food Science and Nutrition 2003;32:1088-94. https://doi.org/10.3746/jkfn.2003.32.7.1088
  6. Ham SS, Oh SW, Kim YK, Shin KS, Chang HY, Chung GH. Antioxidant and genotoxic inhibition activity of ethanol extract from the Inonotus obliquus. Journal of Korean Society of Food Science and Nutrition 2003;32:1071-5. https://doi.org/10.3746/jkfn.2003.32.7.1071
  7. Kahlos K, Hiltunen R, Schantz MV. $3{\beta}$-Hydroxy-lanosta-8,24-dien-21-al, a new triterpene from Inontus obliquus. Planta Med 1984;50:197-8. https://doi.org/10.1055/s-2007-969674
  8. Ichmura T, Watanave O, Maruyama S. Inhibition of HIV-1 protease by water-soluble lignin-like substance from an edible mushroom Fuscoporia obliqua. Biosci Biotechnol Biochem 1998;62:575-7. https://doi.org/10.1271/bbb.62.575
  9. Nakata T, Yamada T, Taji S, Ohishi H, Wada SI, Tokuda H, Sakuma K, Tanaka R. Structure determination of inonotsuoxides A and B and in vivo anti-tumor promoting activity of inotodiol from the sclerotia of Inonotus obliquus. Bioorg Med Chem 2007;15:257-64. https://doi.org/10.1016/j.bmc.2006.09.064
  10. Lee SH, Hwang HS, Yun JW. Antitumor activity of water extract of a mushroom, Inonotus obliquus, against HT-29 human colon cancer cells. Phytother Res 2009;23:1784-9. https://doi.org/10.1002/ptr.2836
  11. Ham SS, Kim SH, Moon SY, Chung MJ, Cui CB, Han EK, Chung CK, Choe M. Antimutagenic effects of subfractions of Chaga mushroom (Inonotus obliquus) extract. Mutat Res 2009; 672:55-9. https://doi.org/10.1016/j.mrgentox.2008.10.002
  12. Chung MJ, Walker PA, Brown RW, Hogstrand C. Zinc-mediated gene expression offers protection against $H_2O_2$-induced cytotoxicity. Toxicol Appl Pharmacol 2005;205:225-36. https://doi.org/10.1016/j.taap.2004.10.008
  13. Ham YA, Choi HJ, Kim SH, Chung MJ, Ham SS. Antimutagenic and antitumor effects of Adenophora triphylla extracts. Journal of Korean Society of Food Science and Nutrition 2009;38:25-31. https://doi.org/10.3746/jkfn.2009.38.1.025
  14. Maeda N, Kokai Y, Ohtani S, Hada T, Yoshida H, Mizushina Y. Inhibitory effects of preventive and curative orally administered spinach glycoglycerolipid fraction on the tumor growth of sarcoma and colon in mouse graft models. Food Chem 2009;112: 205-10. https://doi.org/10.1016/j.foodchem.2008.05.059
  15. Oh HT, Chung MJ, Kim SH, Choi HJ, Ham SS. Masou salmon (Oncorhynchus masou) ethanol extract decrease 3-hydroxy-3-methylglutaryl coenzyme A reductase expression in diet-induced obese mice. Nutr Res 2009;29:123-9. https://doi.org/10.1016/j.nutres.2008.11.006
  16. Kahlos K, Hiltunen R. Identification of some lanostane type triterpenes from Inonotus obliquus. Acta Pharmaceutica Fennica 1983;92:220-2.
  17. Mizuno T, Zhuang C, Abe K, Okamoto H, Kiho T, Ukai S, Leclerc S, Meijer L. Antitumor and hypoglycemic activities of polysaccharides from the Sclerotia and Mycelia of Inonotus obliquus (Pers: Fe.) Pll. (Aphyllophoromycetideae). International Journal of Medicinal Mushrooms 1999;1:301-16. https://doi.org/10.1615/IntJMedMushr.v1.i4.20
  18. Kahlos T, Zhuangas L, Hitunen R. Antitumor activity of some compounds and fractions from an n-hexene extract of Inonotus obliquus. Acta Pharmaceutica Fennica 1987;96:33-40.
  19. Nomura M, Takahashi T, Uesugi A, Tanaka R, Kobayashi S. Inotodiol, a lanostane triterpenoid, from Inonotus obliquus inhibits cell proliferation through caspase-3-dependent apoptosis. Anticancer Res 2008;28:2691-6.
  20. Youn MJ, Kim JK, Park SY, Kim Y, Park C, Kim ES, Park Kl, So HS, Park R. Potential anticancer properties of the water extract of lnonotus obliquus by induction of apoptosis in melanoma B16-F10 cells. J Ethnopharmacol 2009;121:221-8. https://doi.org/10.1016/j.jep.2008.10.016

Cited by

  1. Individual differences on immunostimulatory activity of raw and black garlic extract in human primary immune cells vol.34, pp.4, 2012, https://doi.org/10.3109/08923973.2011.649288
  2. Medicinal mushrooms in supportive cancer therapies: an approach to anti-cancer effects and putative mechanisms of action vol.55, pp.1, 2012, https://doi.org/10.1007/s13225-012-0151-3
  3. Medicinal mushrooms in prevention and control of diabetes mellitus vol.56, pp.1, 2012, https://doi.org/10.1007/s13225-012-0187-4
  4. A novel anti-lymphoma protein RE26 from Rozites emodensis (Berk.) Moser vol.93, pp.3, 2012, https://doi.org/10.1007/s00253-011-3450-9
  5. Progress on Understanding the Anticancer Mechanisms of Medicinal Mushroom: Inonotus Obliquus vol.14, pp.3, 2013, https://doi.org/10.7314/APJCP.2013.14.3.1571
  6. Inotodiol Inhabits Proliferation and Induces Apoptosis through Modulating Expression of cyclinE, p27, bcl-2, and bax in Human Cervical Cancer HeLa Cells vol.15, pp.7, 2014, https://doi.org/10.7314/APJCP.2014.15.7.3195
  7. Estonian folk traditional experiences on natural anticancer remedies: From past to the future vol.52, pp.7, 2014, https://doi.org/10.3109/13880209.2013.871641
  8. A5E promotes Cell growth Arrest and Apoptosis in Non Small Cell Lung Cancer vol.57, pp.2, 2014, https://doi.org/10.3839/jabc.2014.017
  9. Compositions and Anti-Tumor Activity of Pyropolyporus fomentarius Petroleum Ether Fraction In Vitro and In Vivo vol.9, pp.10, 2014, https://doi.org/10.1371/journal.pone.0109599
  10. Investigation of Chaga Melanin. II. Composition of Hydrocarbon Fraction vol.49, pp.8, 2015, https://doi.org/10.1007/s11094-015-1323-8
  11. cell cycle arrest in HT-29 human colon cancer cells vol.9, pp.2, 2015, https://doi.org/10.4162/nrp.2015.9.2.111
  12. Chemical composition and biological activity of triterpenes and steroids of chaga mushroom vol.10, pp.1, 2016, https://doi.org/10.1134/S1990750816010108
  13. Anti-tumor effect of Inonotus obliquus in xenograft animals with EBV+human gastric carcinoma vol.52, pp.4, 2016, https://doi.org/10.7845/kjm.2016.6054
  14. Golden Needle Mushroom: A Culinary Medicine with Evidenced-Based Biological Activities and Health Promoting Properties vol.7, pp.1663-9812, 2016, https://doi.org/10.3389/fphar.2016.00474
  15. ), a Future Potential Medicinal Fungus in Oncology? A Chemical Study and a Comparison of the Cytotoxicity Against Human Lung Adenocarcinoma Cells (A549) and Human Bronchial Epithelial Cells (BEAS-2B) vol.17, pp.3, 2018, https://doi.org/10.1177/1534735418757912
  16. Orally administered aqueous extract of Inonotus obliquus ameliorates acute inflammation in dextran sulfate sodium (DSS)-induced colitis in mice vol.143, pp.2, 2010, https://doi.org/10.1016/j.jep.2012.07.008
  17. Hematological and Serum Biochemical Parameters of Korean Native Goats Fed with Spent Mushroom Substrate vol.7, pp.11, 2010, https://doi.org/10.3923/ajava.2012.1139.1147
  18. Ethanol extracts from the mushroomInonotus obliquus(Chaga) alter melanoma cell viability and morphology vol.84, pp.2, 2010, https://doi.org/10.1893/0005-3155-84.2.74
  19. Medicinal Plants Combating Against Cancer - a Green Anticancer Approach vol.15, pp.11, 2014, https://doi.org/10.7314/apjcp.2014.15.11.4385
  20. Ergosterol peroxide from Chaga mushroom (Inonotus obliquus) exhibits anti-cancer activity by down-regulation of the β-catenin pathway in colorectal cancer vol.173, pp.None, 2010, https://doi.org/10.1016/j.jep.2015.07.030
  21. Medicinal mushrooms as an attractive new source of natural compounds for future cancer therapy vol.9, pp.49, 2010, https://doi.org/10.18632/oncotarget.25660
  22. Inonotus obliquus 액체배양을 통한 균사체 및 다당체 생산을 위한 최적 배양공정 개발 vol.33, pp.2, 2018, https://doi.org/10.7841/ksbbj.2018.33.2.110
  23. The pharmacological potential and possible molecular mechanisms of action of Inonotus obliquus from preclinical studies vol.33, pp.8, 2010, https://doi.org/10.1002/ptr.6384
  24. RNA-Seq de Novo Assembly and Differential Transcriptome Analysis of Chaga (Inonotus obliquus) Cultured with Different Betulin Sources and the Regulation of Genes Involved in Terpenoid Biosynthesis vol.20, pp.18, 2010, https://doi.org/10.3390/ijms20184334
  25. Quality control and evaluation of Inonotus obliquus using HPLC method with novel marker compounds vol.11, pp.1, 2010, https://doi.org/10.1186/s40543-020-00249-z
  26. Common garlic (Allium sativum L.) has potent Anti-Bacillus anthracis activity vol.264, pp.None, 2010, https://doi.org/10.1016/j.jep.2020.113230
  27. Medicinal Properties and Bioactive Compounds from Wild Mushrooms Native to North America vol.26, pp.2, 2021, https://doi.org/10.3390/molecules26020251
  28. Recent Developments in Inonotus obliquus (Chaga mushroom) Polysaccharides: Isolation, Structural Characteristics, Biological Activities and Application vol.13, pp.9, 2021, https://doi.org/10.3390/polym13091441
  29. Inonotus obliquus - from folk medicine to clinical use vol.11, pp.4, 2010, https://doi.org/10.1016/j.jtcme.2020.08.003
  30. Role of Phytochemicals in Cancer Chemoprevention: Insights vol.10, pp.9, 2010, https://doi.org/10.3390/antiox10091455