Tumor Biology

, Volume 37, Issue 3, pp 2789–2804 | Cite as

Misconstrued versatility of Ganoderma lucidum: a key player in multi-targeted cellular signaling

  • Balraj Singh Gill
  • Prateek Sharma
  • Raj Kumar
  • Sanjeev Kumar


A Basidiomycetes fungus belonging to polypore family of mushrooms, Ganoderma lucidum (GL), has been known since a long time for their myriad therapeutic indications. Renowned as an invaluable resource of cardinal mycoconstituents they encompass numerous terpenoids polysaccharides and proteins. Possessing the therapeutically potent lanosteroidal skeleton, terpenoids are upheld for their invariable participation in therapeutically diverse bioactivities. Polysaccharides and proteins exhibiting distinguishable bioactivities provide this oriental mushroom with additional edges over immune function and anti-cancer potential. This review is a concerted effort to throw light upon the therapeutic versatility of the fungus, shadowed by various other natural products. An effort has been made towards conglomerating the mycoconstituents decisive for the many activities portrayed by this fungus. More importantly, this review seeks to fathom the inextricable role played by derivatives in modulating signaling cascades such as downregulation of various mitogenic pathways, inhibiting growth factors, or upregulating certain pathways enhancing cellular integrity.


Ganoderma lucidum Terpenoids Polysaccharides Ganoderic acid (GA) Cancer 



BSG, PS, RK and SK thank Central University of Punjab, Bathinda, for providing the necessary facilities to carry out the present work. The authors acknowledge and thank Dr. Alpana Saini for assistance in editing the article.

Compliance with ethical standards

Conflicts of interests



  1. 1.
    Correia-da-Silva M, Sousa E, Pinto MM. Emerging sulfated flavonoids and other polyphenols as drugs: nature as an inspiration. Med Res Rev. 2013;34(2):223–79.PubMedCrossRefGoogle Scholar
  2. 2.
    Tavakoli J, Miar S, Zadehzare MM, Akbari H. Evaluation of effectiveness of herbal medication in cancer care: a review study. Iran J Cancer Prev. 2012;5(3):144–56.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Moncalvo J. Systematics of Ganoderma 2. In: Flood J, Bridge PD, Holderness M, editors. Ganoderma diseases of perennial crops. U.S.A: CBAI Publishing; 2000. p. 23.CrossRefGoogle Scholar
  4. 4.
    Bhosle S, Ranadive K, Bapat G, Garad S, Deshpande G, Vaidya J. Taxonomy and diversity of Ganoderma from the Western parts of Maharashtra (India). Mycosphere. 2010;1(3):249–62.Google Scholar
  5. 5.
    Jones K. Reishi mushroom: ancient medicine in modern times. J Altern Complement Med. 1998;4(4):256–66.CrossRefGoogle Scholar
  6. 6.
    Cao Y, Wu S-H, Dai Y-C. Species clarification of the prize medicinal Ganoderma mushroom “Lingzhi”. Fungal Divers. 2012;56(1):49–62.CrossRefGoogle Scholar
  7. 7.
    Xu Z, Chen X, Zhong Z, Chen L, Wang Y. Ganoderma lucidum polysaccharides: immunomodulation and potential anti-tumor activities. Am J Chin Med. 2011;39(01):15–27.PubMedCrossRefGoogle Scholar
  8. 8.
    Kao C, Jesuthasan AC, Bishop KS, Glucina MP, Ferguson LR. Anti-cancer activities of Ganoderma lucidum: active ingredients and pathways. Funt Foods Health Dis. 2013;3(2):48–65.Google Scholar
  9. 9.
    Fan L, Li J, Deng K, Ai L. Effects of drying methods on the antioxidant activities of polysaccharides extracted from Ganoderma lucidum. Carbohydr Polym. 2012;87(2):1849–54.CrossRefGoogle Scholar
  10. 10.
    Pan D, Zhang D, Wu J, Chen C, Xu Z, Yang H, et al. A novel proteoglycan from Ganoderma lucidum fruiting bodies protects kidney function and ameliorates diabetic nephropathy via its antioxidant activity in C57BL/6 db/db mice. Food Chem Toxicol. 2014;63:111–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Cilerdzic J, Stajic M, Vukojevic J, Duletic-Lausevic S. Oxidative stress and species of genus Ganoderma (higher Basidiomycetes). Int J Med Mushroom. 2013;15(1):21–8.CrossRefGoogle Scholar
  12. 12.
    Sakthivigneswari G, Dharmaraj K. Studies on analysis of few secondary metabolites and antimicrobial activity of Ganoderma lucidum. J Pharm Res. 2013;1(8).Google Scholar
  13. 13.
    Guillamón E, García-Lafuente A, Lozano M, Rostagno MA, Villares A, Martínez JA. Edible mushrooms: role in the prevention of cardiovascular diseases. Fitoterapia. 2010;81(7):715–23.PubMedCrossRefGoogle Scholar
  14. 14.
    Aguirre-Moreno A, Campos-Pena V, del Rio-Portilla F, Herrera-Ruiz M, Leon-Rivera I, Montiel E, et al. Anticonvulsant and neuroprotective effects of oligosaccharides from Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (higher Basidiomycetes). Int J Med Mushrooms. 2013;15(6):555–68.PubMedCrossRefGoogle Scholar
  15. 15.
    Cheng P-G, Phan C-W, Sabaratnam V, Abdullah N, Abdulla MA, Kuppusamy UR. Polysaccharides-rich extract of Ganoderma lucidum (MA Curtis: Fr.) P. Karst accelerates wound healing in streptozotocin-induced diabetic rats. J Evid Based Complement Altern Med. 2013;2013.Google Scholar
  16. 16.
    Kim HW, Kim BK. Biomedicinal triterpenoids of Ganoderma lucidum (Curt.: Fr.) P. Karst. (Aphyllophoromycetideae). Int J Med Mushrooms. 1999;1(2):121–8.CrossRefGoogle Scholar
  17. 17.
    Mckenna D, Hughes K, Jones K. Botanical medicines: the desk reference for major herbal supplements (2002). New York: The Haworth Herbal Press; 2002.Google Scholar
  18. 18.
    Nasir N. Diseases caused by Ganoderma spp. on perennial crops in Pakistan. Mycopathologia. 2005;159(1):119–21.PubMedCrossRefGoogle Scholar
  19. 19.
    Lee I, Ahn B, Choi J, Hattori M, Min B, Bae K. Selective cholinesterase inhibition by lanostane triterpenes from fruiting bodies of Ganoderma lucidum. Bioorg Med Chem Lett. 2011;21(21):6603–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Zhou Y, Qu ZQ, Zeng YS, Lin YK, Li Y, Chung P, et al. Neuroprotective effect of preadministration with Ganoderma lucidum spore on rat hippocampus. Exp Toxicol Pathol. 2012;64(7):673–80.PubMedCrossRefGoogle Scholar
  21. 21.
    Zhang X-Q, Ip FC, Zhang D-M, Chen L-X, Zhang W, Li Y-L, et al. Triterpenoids with neurotrophic activity from Ganoderma lucidum. Nat Prod Rep. 2011;25(17):1607–13.CrossRefGoogle Scholar
  22. 22.
    Huie CW, Di X. Chromatographic and electrophoretic methods for Lingzhi pharmacologically active components. J Chromatogr B. 2004;812(1):241–57.CrossRefGoogle Scholar
  23. 23.
    Borchers AT, Stern JS, Hackman RM, Keen CL, Gershwin ME. Mushrooms, tumors, and immunity. Proc Soc Exp Biol Med. 1999;221(4):281–93.PubMedCrossRefGoogle Scholar
  24. 24.
    Chen AW, Miles PG. Biomedical research and the application of mushroom nutriceuticals from Ganoderma lucidum. Mushroom Biol mushroom Prod. 1996:161–75.Google Scholar
  25. 25.
    Liu GT. Recent advances in research of pharmacology and clinical applications of Ganoderma P. Karst. species (Aphyllophoromycetideae) in China. Int J Med Mushrooms. 1999;1(1).Google Scholar
  26. 26.
    Yadav VR, Prasad S, Sung B, Kannappan R, Aggarwal BB. Targeting inflammatory pathways by triterpenoids for prevention and treatment of cancer. Toxins. 2010;2(10):2428–66.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Yue QX, Song XY, Ma C, Feng LX, Guan SH, Wu WY, et al. Effects of triterpenes from Ganoderma lucidum on protein expression profile of HeLa cells. Phytomedicine. 2010;17(8):606–13.PubMedCrossRefGoogle Scholar
  28. 28.
    Liu J, Shiono J, Shimizu K, Kukita A, Kukita T, Kondo R. Ganoderic acid DM: anti-androgenic osteoclastogenesis inhibitor. Bioorg Med Chem Lett. 2009;19(8):2154–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Yao X, Li G, Xu H, Lü C. Inhibition of the JAK-STAT3 signaling pathway by ganoderic acid A enhances chemosensitivity of HepG2 Cells to cisplatin. Planta Med. 2012;78(16):1740–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Gill BS, Kumar S. Differential algorithms-assisted molecular modeling-based identification of mechanistic binding of ganoderic acids. Med Chem Res. 2015;24(9):3483–93.CrossRefGoogle Scholar
  31. 31.
    Min B-S, Nakamura N, Miyashiro H, Bae KW, Hattori M. Triterpenes from the spores of Ganoderma lucidum and their inhibitory activity against HIV-1 protease. Chem Pharm Bull. 1998;46(10):1607–12.PubMedCrossRefGoogle Scholar
  32. 32.
    Akbar R, Yam WK. Interaction of ganoderic acid on HIV related target: molecular docking studies. Bioinformation. 2011;7(8):413–7.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    El-Mekkawy S, Meselhy MR, Nakamura N, Tezuka Y, Hattori M, Kakiuchi N, et al. Anti-HIV-1 and anti-HIV-1-protease substances from Ganoderma lucidum. Phytochemistry. 1998;49(6):1651–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Hirotani M, Furuya T. Ganoderic acid derivatives, highly oxygenated lanostane-type triterpenoids, from Ganoderma lucidum. Phytochemistry. 1986;25(5):1189–93.CrossRefGoogle Scholar
  35. 35.
    Guesnet J, Guezennec L, Anne B. Use of ganoderic acids as cosmetic agents and for treating or preventing skin disorder. EP; 2003.Google Scholar
  36. 36.
    Deepalakshmi K, Mirunalini S. Therapeutic properties and current medical usage of medicinal mushroom: Ganoderma lucidum. Int J Pharm Sci Res. 2011;2:1922–9.Google Scholar
  37. 37.
    Thyagarajan A, Jedinak A, Nguyen H, Terry C, Baldridge LA, Jiang J, et al. Triterpenes from Ganoderma lucidum induce autophagy in colon cancer through the inhibition of p38 mitogen-activated kinase (p38 MAPK). Nutr Cancer. 2010;62(5):630–40.PubMedCrossRefGoogle Scholar
  38. 38.
    Xu J-W, Zhao W, Zhong J-J. Biotechnological production and application of ganoderic acids. Appl Microbiol Biotechnol. 2010;87(2):457–66.PubMedCrossRefGoogle Scholar
  39. 39.
    Chen N-H, Zhong J-J. Ganoderic acid Me induces G arrest in wild-type p53 human tumor cells while G/S transition arrest in p53-null cells. Process Biochem. 2009;44(8):928–33.CrossRefGoogle Scholar
  40. 40.
    Zhou L, Shi P, Chen NH, Zhong J-J. Ganoderic acid Me induces apoptosis through mitochondria dysfunctions in human colon carcinoma cells. Process Biochem. 2011;46(1):219–25.CrossRefGoogle Scholar
  41. 41.
    Kanda H, Da Y, Sakamoto M, Fujii M, Hirai Y, Yamazaki K. The biologically active constituents of Ganoderma lucidum (Fr.) Karst. Histamine release-inhibitory triterpenes. Chem Pharm Bull. 1985;33(4):1367–74.CrossRefGoogle Scholar
  42. 42.
    Wasser SP. Reishi or Lingzhi (Ganoderma lucidum). Encycl Diet Suppl. 2005:603–22.Google Scholar
  43. 43.
    Wu GS, Lu JJ, Guo JJ, Li YB, Tan W, Dang YY, et al. Ganoderic acid DM, a natural triterpenoid, induces DNA damage, G1 cell cycle arrest and apoptosis in human breast cancer cells. Fitoterapia. 2012;83(2):408–14.PubMedCrossRefGoogle Scholar
  44. 44.
    Sheena N, Ajith T, Janardhanan K. Anti-inflammatory and anti-nociceptive activities of Ganoderma lucidum occurring in South India. Pharm Biol. 2003;41(4):301–4.CrossRefGoogle Scholar
  45. 45.
    Joseph S, Sabulal B, George V, Smina TP, Janardhanan KK. Antioxidative and antiinflammatory activities of the chloroform extract of Ganoderma lucidum found in South India. Sci Pharm. 2009;77:111–21.CrossRefGoogle Scholar
  46. 46.
    Morigiwa A, Kitabatake K, Fujimoto Y, Ikekawa N. Angiotensin converting enzyme-inhibitory triterpenes from Ganoderma lucidum. Chem Pharm Bull. 1986;34(7):3025–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Hajjaj H, Macé C, Roberts M, Niederberger P, Fay LB. Effect of 26-oxygenosterols from Ganoderma lucidum and their activity as cholesterol synthesis inhibitors. Appl Environ Microbiol. 2005;71(7):3653–8.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Li C, Yin J, Guo F, Zhang D, Sun HH. Ganoderic acid Sz, a new lanostanoid from the mushroom Ganoderma lucidum. Nat Prod Res. 2005;19(5):461–5.PubMedCrossRefGoogle Scholar
  49. 49.
    Tang W, Liu JW, Zhao WM, Wei DZ, Zhong JJ. Ganoderic acid T from Ganoderma lucidum mycelia induces mitochondria mediated apoptosis in lung cancer cells. Life Sci. 2006;80(3):205–11.PubMedCrossRefGoogle Scholar
  50. 50.
    Liu RM, Zhong JJ. Ganoderic acid Mf and S induce mitochondria mediated apoptosis in human cervical carcinoma HeLa cells. Phytomedicine. 2011;18(5):349–55.PubMedCrossRefGoogle Scholar
  51. 51.
    Chen NH, Liu JW, Zhong J-J. Ganoderic acid T inhibits tumor invasion in vitro and in vivo through inhibition of MMP expression. Pharmacol Rep. 2010;62(1):150.PubMedCrossRefGoogle Scholar
  52. 52.
    Fatmawati S, Shimizu K, Kondo R. Inhibition of aldose reductase in vitro by constituents of Ganoderma lucidum. Planta Med. 2010;76(15):1691–3.PubMedCrossRefGoogle Scholar
  53. 53.
    Ouyang JJ, Wang YQ, Tang W. Ganoderic acid restores the sensitivity of multidrug resistance cancer cells to doxorubicin. Adv Mat Res. 2014;834:573–6.Google Scholar
  54. 54.
    Liu RM, Li YB, Zhong J-J. Cytotoxic and pro-apoptotic effects of novel ganoderic acid derivatives on human cervical cancer cells in vitro. Eur J Pharmacol. 2012;681(1):23–33.PubMedCrossRefGoogle Scholar
  55. 55.
    Li YQ, Wang SF. Anti-hepatitis B activities of ganoderic acid from Ganoderma lucidum. Biotechnol Lett. 2006;28(11):837–41.PubMedCrossRefGoogle Scholar
  56. 56.
    Wang JL, Li YB, Qin HL, Zhong JJ. Kinetic study of 7-ethyl ganoderic acid O stability and its importance in the preparative isolation. Biochem Eng J. 2011;53(2):182–6.CrossRefGoogle Scholar
  57. 57.
    Chen N-H, Zhong J-J. p53 is important for the anti-invasion of ganoderic acid T in human carcinoma cells. Phytomedicine. 2011;18(8):719–25.PubMedCrossRefGoogle Scholar
  58. 58.
    Liu J, Shimizu K, Tanaka A, Shinobu W, Ohnuki K, Nakamura T, et al. Target proteins of ganoderic acid DM provides clues to various pharmacological mechanisms. Sci Rep. 2012;2.Google Scholar
  59. 59.
    JunXing L, XiaoGuang L, Lin W, Fei W, ZhiWei Y. Neuroprotective effects of ganoderic acid extract against epilepsy in primary hippocampal neurons. Res Opin Anim Vet Sci. 2013;3(11):420–5.Google Scholar
  60. 60.
    Fatmawati S, Shimizu K, Kondo R, Ganoderol B. A potent α-glucosidase inhibitor isolated from the fruiting body of Ganoderma lucidum. Phytomedicine. 2011;18(12):1053–5.PubMedCrossRefGoogle Scholar
  61. 61.
    Eo SK, Kim YS, Lee CK, Han SS. Antiviral activities of various water and methanol soluble substances isolated from Ganoderma lucidum. J Ethnopharmacol. 1999;68(1):129–36.PubMedCrossRefGoogle Scholar
  62. 62.
    De Silva DD, Rapior S, Sudarman E, Stadler M, Xu J, Alias SA, et al. Bioactive metabolites from macrofungi: ethnopharmacology, biological activities and chemistry. Fungal Divers. 2013;62(1):1–40.CrossRefGoogle Scholar
  63. 63.
    Chen R, Yu D. Development of triterpenes from Ganoderma lucidum. Acta Pharm Sin. 1990;25:940–53.Google Scholar
  64. 64.
    Zhou X, Gong Z, Su Y, Lin J, Tang K. Cordyceps fungi: natural products, pharmacological functions and developmental products. J Pharm Pharmacol. 2009;61(3):279–91.PubMedCrossRefGoogle Scholar
  65. 65.
    Kao CH, Jesuthasan AC, Bishop KS, Glucina MP, Ferguson LR. Anti-cancer activities of Ganoderma lucidum: active ingredients and pathways. Funct Foods Health Dis 2. 2013;3(2):48–65.Google Scholar
  66. 66.
    Feng L, Yuan L, Du M, Chen Y, Zhang M-H, Gu J-F, et al. Anti-lung cancer activity through enhancement of immunomodulation and induction of cell apoptosis of total triterpenes extracted from Ganoderma lucidum (Leyss. ex Fr.) Karst. Molecules. 2013;18(8):9966–81.PubMedCrossRefGoogle Scholar
  67. 67.
    Lin S-B, Li C-H, Lee S-S, Kan L-S. Triterpene-enriched extracts from Ganoderma lucidum inhibit growth of hepatoma cells via suppressing protein kinase C, activating mitogen-activated protein kinases and G2-phase cell cycle arrest. Life Sci. 2003;72(21):2381–90.PubMedCrossRefGoogle Scholar
  68. 68.
    Jiang J, Slivova V, Valachovicova T, Harvey K, Sliva D. Ganoderma lucidum inhibits proliferation and induces apoptosis in human prostate cancer cells PC-3. Int J Oncol. 2004;24(5):1093–9.PubMedGoogle Scholar
  69. 69.
    Lin Z-B. Cellular and molecular mechanisms of immuno-modulation by Ganoderma lucidum. J Pharmacol Sci. 2005;99(2):144–53.PubMedCrossRefGoogle Scholar
  70. 70.
    Jiang J, Grieb B, Thyagarajan A, Sliva D. Ganoderic acids suppress growth and invasive behavior of breast cancer cells by modulating AP-1 and NF-κB signaling. Int J Mol Med. 2008;21(5):577–84.PubMedGoogle Scholar
  71. 71.
    Lokody I. Metabolism: cholesterol promotes breast cancer growth. Nat Rev Cancer. 2014;14(1):11.Google Scholar
  72. 72.
    Komoda Y, Shimizu M, Sonoda Y, Sato Y. Ganoderic acid and its derivatives as cholesterol synthesis inhibitors. Chem Pharm Bull. 1989;37(2):531–3.PubMedCrossRefGoogle Scholar
  73. 73.
    Wu TS, Shi LS, Kuo SC. Cytotoxicity of Ganoderma lucidum triterpenes. J Nat Prod. 2001;64(8):1121–2.PubMedCrossRefGoogle Scholar
  74. 74.
    Liu YW, Gao J-L, Guan J, Qian Z-M, Feng K, Li S-P. Evaluation of antiproliferative activities and action mechanisms of extracts from two species of Ganoderma on tumor cell lines. J Agric Food Chem. 2009;57(8):3087–93.PubMedCrossRefGoogle Scholar
  75. 75.
    Chen NH, Liu JW, Zhong J-J. Ganoderic acid Me inhibits tumor invasion through down-regulating matrix metalloproteinases 2/9 gene expression. J Pharmacol Sci. 2008;108(2):212–6.PubMedCrossRefGoogle Scholar
  76. 76.
    Gao JJ, Min BS, Ahn EM, Nakamura N, Lee HK, Hattori M. New triterpene aldehydes, lucialdehydes A—C, from Ganoderma lucidum and their cytotoxicity against murine and human tumor cells. Chem Pharm Bull. 2002;50(6):837–40.PubMedCrossRefGoogle Scholar
  77. 77.
    Min BS, Gao JJ, Nakamura N, Hattori M. Triterpenes from the spores of Ganoderma lucidum and their cytotoxicity against meth-A and LLC tumor cells. Chem Pharm Bull. 2000;48(7):1026–33.PubMedCrossRefGoogle Scholar
  78. 78.
    Zhu M, Chang Q, Wong LK, Chong FS, Li RC. Triterpene antioxidants from Ganoderma lucidum. Phytother Res. 1999;13(6):529–31.PubMedCrossRefGoogle Scholar
  79. 79.
    Wang G, Zhao J, Liu J, Huang Y, Zhong J-J, Tang W. Enhancement of IL-2 and IFN-γ expression and NK cells activity involved in the anti-tumor effect of ganoderic acid Me in vivo. Int Immunopharmacol. 2007;7(6):864–70.PubMedCrossRefGoogle Scholar
  80. 80.
    Kim HW, Kim BK. Biomedicinal triterpenoids of Ganoderma lucidum (Curt.: Fr.) P. Karst.(Aphyllophoromycetideae). Int J Med Mushrooms. 1999;1(2).Google Scholar
  81. 81.
    Liu C, Song Y, Yang N, Tversky JR, Reid-Adam J, Li X-M. Ganoderic acid β suppressed Th2 responses and induced Th1/Tregs in cultures of peripheral blood mononuclear cells from asthmatic patients. J Allergy Clin Immunol. 2013;131(2):AB1-AB.CrossRefGoogle Scholar
  82. 82.
    Agrawal DK, Shao Z. Pathogenesis of allergic airway inflammation. Curr Allergy Asthma Rep. 2010;10(1):39–48.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Wang CN, Chen JC, Shiao MS, Wang CT. The aggregation of human platelet induced by ganodermic acid S. BBA-Biomembranes. 1989;986(1):151–60.PubMedCrossRefGoogle Scholar
  84. 84.
    Su CY, Shiao MS, Wang CT. Differential effects of ganodermic acid S on the thromboxane A signaling pathways in human platelets. Biochem Pharmacol. 1999;58(4):587–95.PubMedCrossRefGoogle Scholar
  85. 85.
    Li CH, Chen PY, Chang UM, Kan LS, Fang WH, Tsai KS, et al. Ganoderic acid X, a lanostanoid triterpene, inhibits topoisomerases and induces apoptosis of cancer cells. Life Sci. 2005;77(3):252–65.PubMedCrossRefGoogle Scholar
  86. 86.
    Yue QX, Cao ZW, Guan SH, Liu XH, Tao L, Wu WY, et al. Proteomics characterization of the cytotoxicity mechanism of ganoderic acid D and computer-automated estimation of the possible drug target network. Mol Cell Proteomics. 2008;7(5):949–61.PubMedCrossRefGoogle Scholar
  87. 87.
    Harhaji Trajković LM, Mijatović SA, Maksimović-Ivanić DD, Stojanović ID, Momčilović MB, Tufegdžić SJ, et al. Anticancer properties of Ganoderma lucidum methanol extracts in vitro and in vivo. Nutr Cancer. 2009;61(5):696–707.PubMedCrossRefGoogle Scholar
  88. 88.
    Wen T. The inhibition effect of triterpenoid in Ganoderma on topoisomerase I. J Shanghai Inst Technol. 2011;2:001.Google Scholar
  89. 89.
    Hossain A, Radwan FF, Doonan BP, God JM, Zhang L, Bell PD, et al. A possible cross-talk between autophagy and apoptosis in generating an immune response in melanoma. Apoptosis. 2012;17(10):1066–78.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Yoon SY, Eo SK, Kim YS, Lee CK, Han SS. Antimicrobial activity of Ganoderma lucidum extract alone and in combination with some antibiotics. Arch Pharmacal Res. 1994;17(6):438–42.CrossRefGoogle Scholar
  91. 91.
    Keypour S, Riahi H, Moradali M-F, Rafati H. Investigation of the antibacterial activity of a chloroform extract of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (W. Curt.: Fr.) P. Karst.(Aphyllophoromycetideae), from Iran. Int J Med Mushrooms. 2008;10(4).Google Scholar
  92. 92.
    Johnson B, Doonan B, Radwan FF, Haque A. Ganoderic acid DM: an alternative agent for the treatment of advanced prostate cancer. Open Prost Cancer J. 2010;3:78–85.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Miyamoto I, Liu J, Shimizu K, Sato M, Kukita A, Kukita T, et al. Regulation of osteoclastogenesis by ganoderic acid DM isolated from Ganoderma lucidum. Eur J Pharmacol. 2009;602(1):1–7.PubMedCrossRefGoogle Scholar
  94. 94.
    Mor A, Philips MR. Compartmentalized ras/mapk signaling. Annu Rev Immunol. 2006;24:771–800.PubMedCrossRefGoogle Scholar
  95. 95.
    Morgensztern D, McLeod HL. PI3K/Akt/mTOR pathway as a target for cancer therapy. Anti-cancer drug. 2005;16(8):797–803.CrossRefGoogle Scholar
  96. 96.
    Zoncu R, Efeyan A, Sabatini DM. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol. 2011;12(1):21–35.PubMedCrossRefGoogle Scholar
  97. 97.
    Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R. Diabetes and cancer. Endoc Relat Cancer. 2009;16(4):1103–23.CrossRefGoogle Scholar
  98. 98.
    Vermeulen K, Van Bockstaele DR, Berneman ZN. The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 2003;36(3):131–49.PubMedCrossRefGoogle Scholar
  99. 99.
    Chang CJ, Chen YYM, Lu CC, Lin CS, Martel J, Tsai S-H, et al. Ganoderma lucidum stimulates NK cell cytotoxicity by inducing NKG2D/NCR activation and secretion of perforin and granulysin. J Innate Immun. 2013:1753425913491789.Google Scholar
  100. 100.
    Suarez Arroyo IJ, Rosario Acevedo R, Aguilar Perez A, Clemente PL, Cubano LA, Serrano J, et al. Anti-tumor effects of Ganoderma lucidum (Reishi) in inflammatory breast cancer in in vivo and in vitro models. PLoS One. 2013;8(2), e57431.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Haniadka R, Popouri S, Palatty PL, Arora R, Baliga MS. Medicinal plants as antiemetics in the treatment of cancer: a review. Integr Cancer Ther. 2012;11(1):18–28.PubMedCrossRefGoogle Scholar
  102. 102.
    Bao P-P, Lu W, Cui Y, Zheng Y, Gu K, Chen Z, et al. Ginseng and Ganoderma lucidum use after breast cancer diagnosis and quality of life: a report from the Shanghai Breast Cancer Survival Study. PLoS One. 2012;7(6), e39343.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Santra S, Kaittanis C, Grimm J, Perez JM. Drug/dye-loaded, multifunctional iron oxide nanoparticles for combined targeted cancer therapy and dual optical/magnetic resonance imaging. Small. 2009;5(16):1862–8.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Low PS, Henne WA, Doorneweerd DD. Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases. Acc Chem Res. 2007;41(1):120–9.PubMedCrossRefGoogle Scholar
  105. 105.
    Li N, Hu YL, He CX, Hu CJ, Zhou J, Tang GP, et al. Preparation, characterisation and anti-tumour activity of Ganoderma lucidum polysaccharide nanoparticles. J Pharm Pharmacol. 2010;62(1):139–44.PubMedCrossRefGoogle Scholar
  106. 106.
    Kennedy EM, P’Pool SJ, Jiang J, Sliva D, Minto RE. Semisynthesis and biological evaluation of ganodermanontriol and its stereoisomeric triols. J Nat Prod. 2011;74(11):2332–7.PubMedCrossRefGoogle Scholar
  107. 107.
    Jedinak A, Thyagarajan-Sahu A, Jiang J, Sliva D. Ganodermanontriol, a lanostanoid triterpene from Ganoderma lucidum, suppresses growth of colon cancer cells through ss-catenin signaling. Int J Oncol. 2011;38(3):761–7.PubMedGoogle Scholar
  108. 108.
    Liu J, Shimizu K, Kondo R. The effects of Ganoderma alcohols isolated from Ganoderma lucidum on the androgen receptor binding and the growth of LNCaP cells. Fitoterapia. 2010;81(8):1067–72.PubMedCrossRefGoogle Scholar
  109. 109.
    Chang U-M, Li C-H, Lin L-I, Huang C-P, Kan L-S, Lin S-B. Ganoderiol F, a Ganoderma triterpene, induces senescence in hepatoma HepG2 cells. Life Sci. 2006;79(12):1129–39.PubMedCrossRefGoogle Scholar
  110. 110.
    Liu J, Shimizu K, Konishi F, Kumamoto S, Kondo R. The anti-androgen effect of ganoderol B isolated from the fruiting body of Ganoderma lucidum. Bioorg Med Chem. 2007;15(14):4966–72.PubMedCrossRefGoogle Scholar
  111. 111.
    Teng BS, Wang CD, Yang HJ, Wu JS, Zhang D, Zheng M, et al. A protein tyrosine phosphatase 1B activity inhibitor from the fruiting bodies of Ganoderma lucidum (Fr.) Karst and its hypoglycemic potency on streptozotocin-induced type 2 diabetic mice. J Agr Food Chem. 2011;59(12):6492–500.CrossRefGoogle Scholar
  112. 112.
    Negi A, Pandey AK, Joshi G, Agnihotri V. Impact of protein tyrosine phosphate on cancer metastasis: an overview. World J Pharm Res Technol. 2013;1(2):118–30.Google Scholar
  113. 113.
    Cuong TD, Hung TM, Lee JH, Woo MH, Choi JS, Kim J, et al. Inhibitory effect on NO production of triterpenes from the fruiting bodies of Ganoderma lucidum. Bioorg Med Chem Lett. 2013;23(5):1428–32.PubMedCrossRefGoogle Scholar
  114. 114.
    Babitskaya V, Shcherba V, Puchkova T, Smirnov D. Polysaccharides of Ganoderma lucidum: factors affecting their production. Appl Biochem Microbiol. 2005;41(2):169–73.CrossRefGoogle Scholar
  115. 115.
    Sanodiya BS, Thakur GS, Baghel RK, Prasad G, Bisen P. Ganoderma lucidum: a potent pharmacological macrofungus. Curr Pharm Biotechnol. 2009;10(8):717–42.PubMedCrossRefGoogle Scholar
  116. 116.
    Peng Y, Zhang L, Zeng F, Kennedy JF. Structure and antitumor activities of the water-soluble polysaccharides from Ganoderma tsugae mycelium. Carbohydr Polym. 2005;59(3):385–92.CrossRefGoogle Scholar
  117. 117.
    Yang Q, Wang S, Xie Y, Sun J, Wang J. HPLC analysis of Ganoderma lucidum polysaccharides and its effect on antioxidant enzymes activity and Bax, Bcl-2 expression. Int J Biol Macromol. 2010;46(2):167–72.PubMedCrossRefGoogle Scholar
  118. 118.
    Bao X-F, Wang X-S, Dong Q, Fang J-N, Li X-Y. Structural features of immunologically active polysaccharides from Ganoderma lucidum. Phytochemistry. 2002;59(2):175–81.PubMedCrossRefGoogle Scholar
  119. 119.
    Hsu J-W, Huang H-C, Chen S-T, Wong C-H, Juan H-F. Ganoderma lucidum polysaccharides induce macrophage-like differentiation in human leukemia THP-1 cells via caspase and p53 activation. J Evid Based Complement Altern Med. 2011;2011.Google Scholar
  120. 120.
    Zhang Q, Lin Z. The antitumor activity of Ganoderma lucidum (Curt Fr) P Karst (Lingzhi) (Aphyllophoromycetideae) polysaccharides is related to tumor necrosis factor-α and interferon-γ. Int J Med Mushroom. 1999;1(1):207–15.CrossRefGoogle Scholar
  121. 121.
    Liu W, Wang H, Pang X, Yao W, Gao X. Characterization and antioxidant activity of two low-molecular-weight polysaccharides purified from the fruiting bodies of Ganoderma lucidum. Int J Biol Macromol. 2010;46(4):451–7.PubMedCrossRefGoogle Scholar
  122. 122.
    Gao Y, Zhou S, Jiang W, Huang M, Dai X. Effects of Ganopoly® (a Ganoderma lucidum polysaccharide extract) on the immune functions in advanced-stage cancer patients. Immunol Invest. 2003;32(3):201–15.PubMedCrossRefGoogle Scholar
  123. 123.
    Sone Y, Okuda R, Wada N, Kishida E, Misaki A. Structures and antitumor activities of the polysaccharides isolated from fruiting body and the growing culture of mycelium of Ganoderma lucidum. Agric Biol Chem. 1985;9:2641–53.Google Scholar
  124. 124.
    Sun J, He H, Xie BJ. Novel antioxidant peptides from fermented mushroom Ganoderma lucidum. J Agr Food Chem. 2004;52(21):6646–52.CrossRefGoogle Scholar
  125. 125.
    Jia J, Zhang X, Hu YS, Wu Y, Wang QZ, Li NN, et al. Evaluation of in vivo antioxidant activities of Ganoderma lucidum polysaccharides in STZ-diabetic rats. Food Chem. 2009;115(1):32–6.CrossRefGoogle Scholar
  126. 126.
    Zhao L, Dong Y, Chen G, Hu Q. Extraction, purification, characterization and antitumor activity of polysaccharides from Ganoderma lucidum. Carbohydr Polym. 2010;80(3):783–9.CrossRefGoogle Scholar
  127. 127.
    Chen Y, Xie MY, Nie SP, Li C, Wang YX. Purification, composition analysis and antioxidant activity of a polysaccharide from the fruiting bodies of Ganoderma atrum. Food Chem. 2008;107(1):231–41.CrossRefGoogle Scholar
  128. 128.
    Lee JM, Kwon H, Jeong H, Lee JW, Lee SY, Baek SJ, et al. Inhibition of lipid peroxidation and oxidative DNA damage by Ganoderma lucidum. Phytother Res. 2001;15(3):245–9.PubMedCrossRefGoogle Scholar
  129. 129.
    Yang B-K, Wilson MA, Cho K, Song C-H. Hypoglycemic effect of exo-and endo-biopolymers produced by submerged mycelial culture of Ganoderma lucidum in streptozotocin-induced diabetic rats. Appl Microbiol Biotechnol. 2004;14(5):972–7.Google Scholar
  130. 130.
    Gao Y, Lan J, Dai X, Ye J, Zhou S. A phase I/II study of Lingzhi mushroom Ganoderma lucidum (W. Curt.: Fr.) Lloyd (Aphyllophoromycetideae) extract in patients with type ii diabetes mellitus. Int J Med Mushrooms. 2004;6(1).Google Scholar
  131. 131.
    Hikino H, Konno C, Mirin Y, Hayashi T. Isolation and hypoglycemic activity of ganoderans A and B, glycans of Ganoderma lucidum fruit bodies. Planta Med. 1985;51(04):339–40.PubMedCrossRefGoogle Scholar
  132. 132.
    Seto S, Lam T, Tam H, Au A, Chan S, Wu J, et al. Novel hypoglycemic effects of Ganoderma lucidum water-extract in obese/diabetic mice. Phytomedicine. 2009;16(5):426–36.PubMedCrossRefGoogle Scholar
  133. 133.
    Meng G, Zhu H, Yang S, Wu F, Zheng H, Chen E, et al. Attenuating effects of Ganoderma lucidum polysaccharides on myocardial collagen cross-linking relates to advanced glycation end product and antioxidant enzymes in high-fat-diet and streptozotocin-induced diabetic rats. Carbohydr Polym. 2011;84(1):180–5.CrossRefGoogle Scholar
  134. 134.
    He CY, Li WD, Guo SX, Lin SQ, Lin ZB. Effect of polysaccharides from Ganoderma lucidum on streptozotocin-induced diabetic nephropathy in mice. J Asian Nat Prod Res. 2006;8(8):705–11.PubMedCrossRefGoogle Scholar
  135. 135.
    Zhang H-N, Lin Z-B. Hypoglycemic effect of Ganoderma lucidum polysaccharides. Acta Pharmacol Sin. 2004;25(2):191–5.PubMedGoogle Scholar
  136. 136.
    Li F, Zhang Y, Zhong Z. Antihyperglycemic effect of Ganoderma lucidum polysaccharides on streptozotocin-induced diabetic mice. Intl J Mol Sci. 2011;12(9):6135–45.CrossRefGoogle Scholar
  137. 137.
    Lin CY, Chen YH, Lin CY, Hsu HY, Wang SH, Liang CJ, et al. Ganoderma lucidum polysaccharides attenuate endotoxin-induced intercellular cell adhesion molecule-1 expression in cultured smooth muscle cells and in the neointima in mice. J Agric Food Chem. 2010;58(17):9563–71.PubMedCrossRefGoogle Scholar
  138. 138.
    Liu J, Yang F, Ye L-B, Yang X-J, Timani KA, Zheng Y, et al. Possible mode of action of antiherpetic activities of a proteoglycan isolated from the mycelia of Ganoderma lucidum in vitro. J Ethnopharmacol. 2004;95(2):265–72.PubMedCrossRefGoogle Scholar
  139. 139.
    Kim YS, Eo SK, Oh KW, Lee CK, Han SS. Antiherpetic activities of acidic protein bound polysacchride isolated from Ganoderma lucidum alone and in combinations with interferons. J Ethnopharmacol. 2000;72(3):451–8.PubMedCrossRefGoogle Scholar
  140. 140.
    Wang YY, Khoo KH, Chen ST, Lin CC, Wong CH, Lin CH. Studies on the immuno-modulating and antitumor activities of Ganoderma lucidum (Reishi) polysaccharides: functional and proteomic analyses of a fucose-containing glycoprotein fraction responsible for the activities. Bioorg Med Chem. 2002;10(4):1057–62.PubMedCrossRefGoogle Scholar
  141. 141.
    Spackman D, Stein W, Moore S. Chromatography of amino acids on sulphonated polystyrene resins. An improved system. Anal Chem. 1958;30:1185–9.CrossRefGoogle Scholar
  142. 142.
    Lin C-H, Hsiao Y-M, Ou C-C, Lin Y-W, Chiu Y-L, Lue K-H, et al. GMI, a Ganoderma immunomodulatory protein, down-regulates tumor necrosis factor α-induced expression of matrix metalloproteinase 9 via NF-κB pathway in human alveolar epithelial A549 cells. J Agri Food Chem. 2010;58(22):12014–21.CrossRefGoogle Scholar
  143. 143.
    Kino K, Yamashita A, Yamaoka K, Watanabe J, Tanaka S, Ko K, et al. Isolation and characterization of a new immunomodulatory protein, ling zhi-8 (LZ-8), from Ganoderma lucidum. J Biol Chem. 1989;264(1):472–8.PubMedGoogle Scholar
  144. 144.
    Chuang CM, Wang HE, Chang CH, Peng CC, Ker YB, Lai JE, et al. Sacchachitin, a novel chitin-polysaccharide conjugate macromolecule present in Ganoderma lucidum: purification, composition, and properties. Pharm Biol. 2013;51(1):84–95.PubMedCrossRefGoogle Scholar
  145. 145.
    Kohsuke K, Toshio S, Watanabe J, Yamashita A, Tsuboi H, Miyajima H, et al. Immunomodulator, LZ-8, prevents antibody production in mice. Int J Immunopharmacol. 1991;13(8):1109–15.CrossRefGoogle Scholar
  146. 146.
    Hsu HY, Kuan YC, Lin TY, Tsao SM, Hsu J, Ma LJ, et al. Reishi protein LZ-8 induces FOXP3. J Evi Based Complement Altern Med. 2013;2013.Google Scholar
  147. 147.
    Wu CT, Lin TY, Hsu HY, Sheu F, Ho C-M, Chen EIT. Ling Zhi-8 mediates p53-dependent growth arrest of lung cancer cells proliferation via the ribosomal protein S7-MDM2-p53 pathway. Carcinogenesis. 2011;32(12):1890–6.PubMedCrossRefGoogle Scholar
  148. 148.
    Liang C, Li H, Zhou H, Zhang S, Liu Z, Zhou Q, et al. Recombinant Lz-8 from Ganoderma lucidum induces endoplasmic reticulum stress-mediated autophagic cell death in SGC-7901 human gastric cancer cells. Oncol Rep. 2012;27(4):1079–89.PubMedGoogle Scholar
  149. 149.
    Ansor NM, Abdullah N, Aminudin N. Anti-angiotensin converting enzyme (ACE) proteins from mycelia of Ganoderma lucidum (Curtis) P. Karst. BMC Complement Altern Med. 2013;13(1):256.CrossRefGoogle Scholar
  150. 150.
    Hsu C-C, Chen C-H, Hsu T-I, Hung J-J, Ko J-L, Zhang B, et al. The 58-kDa microspherule protein (MSP58) represses human telomerase reverse transcriptase (hTERT) gene expression and cell proliferation by interacting with telomerase transcriptional element-interacting factor (TEIF). Biochimica et Biophysica Acta (BBA)- Mol Cell Res. 2013;1843(3):565–79.CrossRefGoogle Scholar
  151. 151.
    Liao CH, Hsiao YM, Hsu CP, Lin MY, Wang JCH, Huang YL, et al. Transcriptionally mediated inhibition of telomerase of fungal immunomodulatory protein from Ganoderma tsugae in A549 human lung adenocarcinoma cell line. Mol Carcinog. 2006;45(4):220–9.PubMedCrossRefGoogle Scholar
  152. 152.
    Ngai PH, Ng T. A mushroom (Ganoderma capense) lectin with spectacular thermostability, potent mitogenic activity on splenocytes, and antiproliferative activity toward tumor cells. Biochem Biophys Res Commun. 2004;314(4):988–93.PubMedCrossRefGoogle Scholar
  153. 153.
    Zhou S, Gao Y, Chan E. Clinical trials for medicinal mushrooms: experience with Ganoderma lucidum (W. Curt.: Fr.) Lloyd (Lingzhi mushroom). Int J Med Mushrooms. 2005;7(1&2).Google Scholar
  154. 154.
    Jin X, Ruiz Beguerie J, Sze DMy, Chan GC. Ganoderma lucidum (Reishi mushroom) for cancer treatment. Cochrane Libr. 2012.Google Scholar
  155. 155.
    Gao Y, Zhou S, Chen G, Dai X, Ye J, Gao H. A phase I/II study of a Ganoderma lucidum (Curt.: Fr.) P. Karst.(Lingzhi, Reishi Mushroom) extract in patients with chronic hepatitis В. Int J Med Mushrooms. 2002;4(4).Google Scholar
  156. 156.
    Wicks SM, Tong R, Wang C-Z, O’Connor M, Karrison T, Li S, et al. Safety and tolerability of Ganoderma lucidum in healthy subjects: a double-blind randomized placebo-controlled trial. Am J Chin Med. 2007;35(03):407–14.PubMedCrossRefGoogle Scholar
  157. 157.
    Noguchi M, Kakuma T, Tomiyasu K, Yamada A, Itoh K, Konishi F, et al. Randomized clinical trial of an ethanol extract of Ganoderma lucidum in men with lower urinary tract symptoms. Asian J Androl. 2008;10(5):777–85.PubMedCrossRefGoogle Scholar
  158. 158.
    Soo TS. Effective dosage of the extract of Ganoderma lucidum in the treatment of various ailments. Mushroom biology and mushroom products. Royse: The Pennsylvania State University; 1996. p. 177–85.Google Scholar
  159. 159.
    Wanmuang H, Leopairut J, Kositchaiwat C, Wananukul W, Bunyaratvej S. Fatal fulminant hepatitis associated with Ganoderma lucidum (Lingzhi) mushroom powder. J Med Assoc Thai. 2007;90(1):179.PubMedGoogle Scholar
  160. 160.
    Kawagishi H, Fukuhara F, Sazuka M, Kawashima A, Mitsubori T, Tomita T. 5′-Deoxy-5′-methylsulphinyladenosine, a platelet aggregation inhibitor from Ganoderma lucidum. Phytochemistry. 1993;32(2):239–41.CrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Balraj Singh Gill
    • 1
  • Prateek Sharma
    • 1
  • Raj Kumar
    • 2
  • Sanjeev Kumar
    • 1
    • 2
  1. 1.Centre for BiosciencesCentral University of PunjabBathindaIndia
  2. 2.Centre for Chemical and Pharmaceutical Sciences, School of Basic and Applied SciencesCentral University of PunjabBathindaIndia

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