Skip to main content

Advertisement

SpringerLink
Log in

The in vitro and in vivo experimental evidences disclose the chemopreventive effects of Ganoderma lucidum on cancer invasion and metastasis

  • Review
  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

The Ganoderma lucidum (Leyss. ex Fr.) Karst, an edible mushroom, has been utilized for centuries in East Asia to prevent or treat various diseases and to reduce the likelihood of cancer invasion and metastasis. The primary bioactive compounds are commonly considered to be polysaccharides and triterpenoids. Evidence that G. lucidum extract and its bioactive compounds may have a potential inhibitory effect on cancer invasion and metastasis is increasingly being reported in the scientific literature. This review assembles and summarizes past publications on the in vitro and in vivo effects of G. lucidum on cancer invasion and metastasis, and concludes that these effects occur through modulation of the phosphorylation of extracellular signal-regulated kinase (ERK1/2), phosphatidylinositol 3-kinase (PI 3-kinase) or Akt kinase (protein kinase B). Activation of these kinases subsequently inhibits the activity or expression of activator protein-1(AP-1) and nuclear factor-kappa B (NF-κB), resulting in the down-regulation of urokinase plaminogen activator (uPA), uPA receptor (uPAR), matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, interleukin (IL)-8, inducible nitric oxide (NO) and β1-integrin as shown in various cell lines or animal models. G. lucidum may be an effective nutraceutical used in the prevention of cancer metastasis. To further elucidate the bioactive components present in G. lucidum and the anti-metastatic mechanisms underlying these compounds, more in vitro and in vivo tests as well as clinical trials are necessary.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

Akt kinase:

Protein kinase B

AP-1:

Activator protein-1

CAM:

Chick chorioallantoic membrane assay

CDK:

Cyclin-dependent kinase

ECM:

Extracellular matrix

ERK1/2:

Extracellular signal regulated kinase

GLE:

G. lucidum extract

GLPP:

G. lucidum polysaccharides peptide

GTE:

Green tea extract

IL:

Interleukin

LLC:

Lewis lung carcinoma

MMP:

Matrix metalloproteinase

MT-1 MMP:

Membrane type 1-MMP

NF-κB:

Nuclear factor-kappa B

NO:

Nitric oxide

PI 3-kinase:

Phosphatidylinositol 3-kinase

PMA:

Phorbol-12-myristate-13-acetate

TGF-β1:

Transforming growth factor-β1

Th1:

T-helper type 1

uPA:

Urokinase plaminogen activator

uPAR:

uPA receptor

VEGF:

Vascular endothelial growth factor

References

  1. Weiss L (1990) Metastatic inefficiency. Adv Cancer Res 54:159–211

    Article  CAS  PubMed  Google Scholar 

  2. Liotta LA, Steeg PS, Stetter-Stevenson WG (1991) Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64:327–336

    Article  CAS  PubMed  Google Scholar 

  3. Condeelis J, Segall JE (2003) Intravital imaging of cell movement in tumours. Nat Rev Cancer 3:921–930

    Article  CAS  PubMed  Google Scholar 

  4. Sliva D (2008) Suppression of cancer invasiveness by dietary compounds. Mini Rev Med Chem 8:677–688

    Article  CAS  PubMed  Google Scholar 

  5. Aarisawa M, Fujita A, Saga M et al (1986) Three new lanostanoids from Ganoderma lucidum. J Nat Prod 49:621–625

    Article  Google Scholar 

  6. Gao YH, Zhou SF (2004) Chemopreventive and tumoricidal properties of Ling Zhi mushroom Ganoderma lucidum (W. Curt.: Fr.) Lloyd (Aphyllophoromycetideae). II. Mechanism considerations. Int J Med Mushrooms 6:219–230

    Article  CAS  Google Scholar 

  7. Gao JJ, Nakamura N, Min BS et al (2004) Quantitative determination of bitter principles in specimens of Ganoderma lucidum using high-performance liquid chromatography and its application to the evaluation of Ganoderma products. Chem Pharm Bull 52:688–695

    Article  CAS  PubMed  Google Scholar 

  8. Lin ZB, Zhang HN (2004) Anti-tumor and immunoregulatory activities of Ganoderma lucidum and its possible mechanisms. Acta Pharmacol Sin 25:1387–1395

    CAS  PubMed  Google Scholar 

  9. Johnston N (2005) Medicinal mushroom cuts off prostate cancer cells’ blood supply. Drug Discov Today 10:23–24

    Article  CAS  Google Scholar 

  10. Liu GQ, Zhang KC (2005) Mechanisms of the anticancer action of Ganoderma lucidum (Leyss. Ex Fr.) Karst.: A new understanding. J Integr Plant Biol 47:129–135

    Article  CAS  Google Scholar 

  11. Yuen JWM, Gohel MDI (2005) Anticancer effects of Ganoderma lucidum: a review of scientific evidence. Nutr Cancer 53:11–17

    Article  CAS  PubMed  Google Scholar 

  12. Paterson RR (2006) Ganoderma—a therapeutic fungal biofactory. Phytochemistry 67:1985–2001

    Article  CAS  PubMed  Google Scholar 

  13. Xie JT, Wang CZ, Wicks S et al (2006) Ganoderma lucidum extract inhibits proliferation of SW 480 human colorectal cancer cells. Exp Oncol 28:25–29

    CAS  PubMed  Google Scholar 

  14. Stanley G, Harvey K, Slivova V et al (2005) Ganoderma lucidum suppresses angiogenesis through the inhibition of secretion of VEGF and TGF-b1 from prostate cancer cells. Biochem Biophys Res Commun 330:46–52

    Article  CAS  PubMed  Google Scholar 

  15. Sliva D, Rizzo D (2002) Phosphatidylinositol 3-kinase and NF-κB regulate motility of invasive MDA-MB-231 human breast cancer cells by the secretion of urokinase-type plasminogen activator. J Biol Chem 277:3150–3157

    Article  CAS  PubMed  Google Scholar 

  16. Teow SS (1997) The effective application of Ganoderma nutriceuticals. In: Kim BK, Moon CK, Kim TS (eds) Recent progress in Ganoderma lucidum research. The Pharmaceutical Society of Korea, Seoul

    Google Scholar 

  17. Wang YY, Khoo KH, Chen ST et al (2002) Studies on the immuno-modulating and anti-tumor activities of Ganoderma lucidum (Reishi). Polysaccharides: functional and proteomic analyses of a fucose-containing glycoprotein fraction responsible for the activities. Bioorgan Med Chem 10:1057–1062

    Article  CAS  Google Scholar 

  18. Yang HL, Zhang KC (2002) The relationship between molecular structure and activity of Ganoderma acids. J Wuxi Univ Light Ind 21:249–253 (in Chinese with an English abstract)

    CAS  Google Scholar 

  19. Ooi VE, Liu F (2000) Immunomodulation and anti-cancer activity of polysaccharideprotein complexes. Curr Med Chem 7:715–729

    Google Scholar 

  20. Wasser SP (2002) Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl Microbiol Biotechnol 60: 258–274

    Google Scholar 

  21. Sullivan R, Smith JE, Rowan NJ (2006) Medicinal mushrooms and cancer therapy: translating a traditional practice into western medicine. Perspect Biol Med 49:159–170

    Article  CAS  PubMed  Google Scholar 

  22. Zhang M, Cui SW, Cheung PCK et al (2007) Antitumor polysaccharides from mushrooms: a review of their isolation process, structural characteristics and antitumor activity. Trends Food Sci Tech 18:4–19

    Article  CAS  Google Scholar 

  23. Hyun JW, Choi EC, Kim BK (1990) Studies on constituents of higher fungi of Korea IXII. Antitumor components of the basidiocarp of Ganoderma lucidum. Korean J Mycol 18:58–69

    CAS  Google Scholar 

  24. Wu TS, Shi LS, Kuo SC (2001) Cytotoxicity of Ganoderma lucidum triterpenes. J Nat Prod 64:1121–1122

    Article  CAS  PubMed  Google Scholar 

  25. Akihisa T, Nakamura Y, Tagata M et al (2007) Ani-inflammatory and anti-tumor-promoting effects of triterpene acids and sterols from the fungus Ganoderma lucidum. Chem Biodivers 4:224–231

    Article  CAS  PubMed  Google Scholar 

  26. Chen Y, Yan Y, Xie MY et al (2008) Development of a chromatographic fingerprint for the chloroform extracts of Ganoderma lucidum by HPLC and LC–MS. J Pharm Biomed Anal 47:469–477

    Article  CAS  PubMed  Google Scholar 

  27. Shiao MS (2003) Natural products of the medicinal fungus Ganoderma lucidum: occurrence, biological activities, and pharmacological functions. Chem Rec 3:172–180

    Article  CAS  PubMed  Google Scholar 

  28. Sliva D (2003) Ganoderma lucidum (Reishi) in cancer treatment. Integr Cancer Ther 2:358–364

    Article  PubMed  Google Scholar 

  29. Sliva D (2006) Ganoderma lucidum in cancer research. Leuk Res 30:767–768

    Article  PubMed  Google Scholar 

  30. Russell R, Paterson M (2006) Ganoderma—A therapeutic fungal biofactory. Phytochemistry 67:1985–2001

    Article  CAS  Google Scholar 

  31. Lee SS, Wei YH, Chen CF et al (1995) Antitumor effects of Ganoderma lucidum. J Chin Med 6:1–12

    Google Scholar 

  32. Nonaka Y, Ishibashi H, Nakai M et al (2008) Effects of the antlered form of Ganoderma lucidum on tumor growth and metastasis in cyclophosphamide-treated mice. Biosci Biotechnol Biochem 72:1399–1408

    Article  CAS  PubMed  Google Scholar 

  33. Allison AC (2000) Immunosuppressive drugs: the first 50 years and a glance forward. Immunopharmacology 47:63–83

    Article  CAS  PubMed  Google Scholar 

  34. Sliva D, Labarrere C, Slivova V et al (2002) Ganoderma lucidum suppresses motility of highly invasive breast and prostate cancer cells. Biochem Biophys Res Commun 298:603–612

    Article  CAS  PubMed  Google Scholar 

  35. Sliva D, Sedlak M, Slivova V et al (2003) Biological activity of spores and dried powder from Ganoderma lucidum for the inhibition of highly invasive human breast and prostate cancer cells. J Altern Complement Med 9:491–497

    Article  PubMed  Google Scholar 

  36. Slivova V, Valachovicova T, Jiang J et al (2004) Ganoderma lucidum inhibits invasiveness of breast cancer cells. J Cancer Integr Med 2:25–30

    Google Scholar 

  37. Thyagarajan A, Zhu J, Sliva D (2007) Combined effect of green tea and Ganoderma lucidum on invasive behavior of breast cancer cells. Int J Oncol 30:963–969

    CAS  PubMed  Google Scholar 

  38. Thyagarajan A, Jiang J, Hopf A et al (2006) Inhibition of oxidative stress-induced invasiveness of cancer cells by Ganoderma lucidum is mediated through the suppression of interleukin-8 secretion. Intl J Mol Med 18:657–664

    CAS  Google Scholar 

  39. Song YS, Kim SH, Sa JH et al (2004) Anti-angiogenesis and inhibitory activity on inducible nitric oxide production of the mushroom Ganoderma lucidum. J Ethnopharmacol 90:17–20

    Article  PubMed  Google Scholar 

  40. Zjawiony JK (2004) Biologically active compounds from Aphyllophorales (Polypore) fungi. J Nat Prod 67:300–310

    Article  CAS  PubMed  Google Scholar 

  41. Jong SC, Birmingham JM (1992) Medicinal benefits of the mushroom Ganoderma. Adv Appl Microbiol 37:101–134

    Article  CAS  PubMed  Google Scholar 

  42. Shiao MS, Lee KR, Lin LJ et al. (1994) Natural products and biological activities of the chinese medicinal fungus Ganoderma lucidum. In: Ho CT, Osawa T, Huang MT, Rosen RT (eds) Food phytochemicals for cancer prevention II: teas, spices and herbs. Oxford University Press, Washington, DC

    Google Scholar 

  43. Chen Y, Xie MY, Gong XFJ (2007) Microwave-assisted extraction used for the isolation of total triterpenoid saponins from Ganoderma atrum. J Food Eng 81:162–170

    Article  CAS  Google Scholar 

  44. Mizuno T, Wang G, Zhang J et al (1995) Reishi, Ganoderma lucidum and Ganoderma tsugae: bioactive substances and medicinal effects. Food Rev Int 11:151–166

    Article  CAS  Google Scholar 

  45. Min BS, Gao JJ, Nakamura N et al (2000) Triterpenes from the spores of Ganoderma lucidum and their cytotoxicity against meth-A and LLC tumor cells. Chem Pharm Bull 48:1026–1033

    CAS  PubMed  Google Scholar 

  46. Adam JK, Odhav B, Bhoola KD (2003) Immune responses in cancer. Food Rev Int 99:113–132

    CAS  Google Scholar 

  47. Cao QZ, Lin ZB (2004) Antitumor and anti-angiogenic activity of Ganoderma lucidum polysaccharides peptide. Acta Pharmacol Sin 25:833–838

    CAS  PubMed  Google Scholar 

  48. Gao YH, Chan E, Zhou SF (2004) Immunomodulating activities of Ganoderma, a mushroom with medicinal properties. Food Rev Int 20:123–161

    Article  CAS  Google Scholar 

  49. Gao YH, Tang WB, Gao H et al (2004) Chemopreventive and tumoricidal properties of Lingzhi mushroom Ganoderma lucidum (W. Curt.:Fr.) Lloyd (Aphyllophorophoromycetideae). I. Preclinical and clinical studies (review). Int J Med Mushroom 6:95–106

    Article  CAS  Google Scholar 

  50. Gao JJ, Min BS, Ahn E et al (2002) New triterpene aldehydes, lucialdehydes A–C, from Ganoderma lucidum and their cytotoxicity against murine and human tumor cells. Chem Pharm Bull 50:837–840

    Article  CAS  PubMed  Google Scholar 

  51. Lin ZB (2005) Cellular and molecular mechanisms of immuno-modulation by Ganoderma lucidum. J Pharmacol Sci 99:144–153

    Article  CAS  PubMed  Google Scholar 

  52. Liu X, Yuan JP, Chung CK et al (2002) Antitumor activity of the sporoderm-broken germinating spores of Ganoderma lucidum. Cancer Lett 182:155–161

    Article  CAS  PubMed  Google Scholar 

  53. Lin LJ, Shiao MS (1989) 13C-NMR correlation of stereochemistry in lanostanoids triterpenes. J Nat Prod 52:595–605

    Article  CAS  Google Scholar 

  54. Lin CN, Tome WP, Won SJ (1990) A lanostanoid of formosan Ganoderma lucidum. Phytochemistry 29:673–675

    Article  CAS  Google Scholar 

  55. Lin CN, Tome WP (1991) Novel cytotoxic principles of formosan Ganoderma lucidum. J Nat Prod 54:998–1002

    Article  CAS  PubMed  Google Scholar 

  56. Kimura Y, Taniguchi M, Baba K (2002) Antitumor and antimetastatic effects on liver of triterpenoid fractions of Ganoderma lucidum: mechanism of action and isolation of an active substance. Anticancer Res 22:3309–3318

    CAS  PubMed  Google Scholar 

  57. Kleiner DE, Stetler-Stevenson WG (1999) Matrix metalloproteinases and metastasis. Cancer Chemother Pharmacol 43:S41–S51

    Article  Google Scholar 

  58. Westermarck J, Kahari VM (1999) Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J 13:781–792

    CAS  PubMed  Google Scholar 

  59. Rao JS (2003) Molecular mechanisms of glioma invasiveness: the role of proteases. Nat Rev Cancer 3:489–501

    Article  CAS  PubMed  Google Scholar 

  60. Basset P, Okada A, Chenard MP et al (1997) Matrix metalloproteinases as stromal effectors of human carcinoma progression: therapeutic implications. Matrix Biol 15:535–541

    Article  CAS  PubMed  Google Scholar 

  61. Nelson AR, Fingleton B, Rothenberg ML et al (2000) Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol 18:1135–1149

    CAS  PubMed  Google Scholar 

  62. Chung TW, Moon SK, Lee YC et al (2002) Enhanced expression of matrix metalloproteinase-9 by hepatitis B virus infection in liver cells. Arch Biochem Biophys 408:147–154

    Article  CAS  PubMed  Google Scholar 

  63. Mazar AP (2001) The urokinase plasminogen activator receptor (uPAR) as a target for the diagnosis and therapy of cancer. Anticancer Drugs 12:387–400

    Article  CAS  PubMed  Google Scholar 

  64. Ikekawa T, Nakanishi M, Uehara N et al (1969) Antitumor activity of aqueous extracts of edible mushrooms. Cancer Res 29:734–735

    CAS  PubMed  Google Scholar 

  65. Folkman J (1989) What is the evidence that tumor are angiogenesis dependent? J Natl Cancer Inst 82:4–6

    Article  Google Scholar 

  66. Kim KJ, Li B, Winer J et al (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumor growth in vivo. Nature 362:841–844

    Article  CAS  PubMed  Google Scholar 

  67. Millauer B, Shawver LK, Plate KH et al (1994) Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant. Nature 367:576–579

    Article  CAS  PubMed  Google Scholar 

  68. Miura T, Yuan L, Sun B et al (2002) Isoflavone aglycon produced by culture of soybean extracts with basidiomycetes and its anti-angiogenic activity. Biosci Biotechnol Biochem 66:2626–2631

    Article  CAS  PubMed  Google Scholar 

  69. Wu QP, Xie YZ, Li SZ et al (2006) Tumor cell adhesion and integrin expression affected by Ganoderma lucidum. Enzyme Microb Tech 40:32–41

    Article  CAS  Google Scholar 

  70. Cao QZ, Lin SQ, Wang SZ (2007) Effect of Ganoderma lucidum polysaccharides peptide on invasion of human lung carcinoma cells in vitro. Beijing Da Xue Xue Bao 39:653–656

    CAS  PubMed  Google Scholar 

  71. Tang W, Gu TY, Zhong JJ (2006) Separation of targeted ganoderic acids from Ganoderma lucidum by reversed phase liquid chromatography with ultraviolet and mass spectrometry detections. Biochem Eng J 32:205–210

    Article  CAS  Google Scholar 

  72. Wang G, Zhao J, Liu JW et al (2007) Enhancement of IL-2 and IFN-gamma expression and NK cells activity involved in the anti-tumor effect of ganoderic acid Me in vivo. Int Immunopharmacol 7:864–870

    Article  CAS  PubMed  Google Scholar 

  73. Chen NH, Liu JW, Zhong JJ (2008) Ganoderic acid Me inhibits tumor invasion through down-regulating matrix metalloproteinases 2/9 gene expression. J Pharmacol Sci 108:212–216

    Article  CAS  PubMed  Google Scholar 

  74. Jiang J, Grieb B, Thyagarajan A et al (2008) Ganoderic acid suppress growth and invasive behavior of breast cancer cells by modulating AP-1 and NF-kappaB signaling. Int J Mol Med 21:577–584

    CAS  PubMed  Google Scholar 

  75. Chen NH, Liu JW, Zhong JJ (2010) Ganoderic acid T inhibits tumor invasion in vitro and in vivo through inhibition of MMP expression. Pharmacol Rep 62:150–163

    Article  PubMed  CAS  Google Scholar 

  76. Weng CJ, Chau CF, Chen KD et al (2007) The anti-invasive effects of lucidenic acids isolated from a new Ganoderma lucidum strain. Mol Nutr Food Res 51:1472–1477

    Article  CAS  PubMed  Google Scholar 

  77. Jiang J, Slivova V, Valachovicova T et al (2004) Ganoderma lucidum inhibits proliferation and induces apoptosis in human prostate cancer cells PC-3. Int J Oncol 24:1093–1100

    CAS  PubMed  Google Scholar 

  78. Weng CJ, Chau CF, Hsieh YS et al (2008) Lucidenic acid inhibit PMA-induced invasion of human hepatoma cells through inactivating MAPK/ERK signal transduction pathway and reducing binding activities of NF-kB and AP-1. Carcinogenesis 29:147–156

    Article  CAS  PubMed  Google Scholar 

  79. Weng CJ, Chau CF, Yen GC et al (2009) Inhibitory effects of Ganoderma lucidum on tumorigenesis and metastasis of human hepatoma cells in cells and animal models. J Agric Food Chem 57:5049–5057

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Graduate Institute of Applied Science of Living, Tainan University of Technology, 529 Jhongjheng Road, Yongkang, Tainan, 71002, Taiwan

    Chia-Jui Weng

  2. Department of Food Science and Biotechnology, National Chung Hsing University, 250 Kuokuang Road, Taichung, 40227, Taiwan

    Gow-Chin Yen

Authors
  1. Chia-Jui Weng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gow-Chin Yen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gow-Chin Yen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Weng, CJ., Yen, GC. The in vitro and in vivo experimental evidences disclose the chemopreventive effects of Ganoderma lucidum on cancer invasion and metastasis. Clin Exp Metastasis 27, 361–369 (2010). https://doi.org/10.1007/s10585-010-9334-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-010-9334-z

Keywords

Search

Navigation