Journal of Natural Medicines

, Volume 71, Issue 2, pp 457–462 | Cite as

Tubulin polymerization-stimulating activity of Ganoderma triterpenoids

  • Toshitaka Kohno
  • Tran Hai-Bang
  • Qinchang Zhu
  • Yhiya Amen
  • Seiichi Sakamoto
  • Hiroyuki Tanaka
  • Satoshi Morimoto
  • Kuniyoshi ShimizuEmail author


Tubulin polymerization is an important target for anticancer therapies. Even though the potential of Ganoderma triterpenoids against various cancer targets had been well documented, studies on their tubulin polymerization-stimulating activity are scarce. This study was conducted to evaluate the effect of Ganoderma triterpenoids on tubulin polymerization. A total of twenty-four compounds were investigated using an in vitro tubulin polymerization assay. Results showed that most of the studied triterpenoids exhibited microtuble-stabilizing activity to different degrees. Among the investigated compounds, ganoderic acid T-Q, ganoderiol F, ganoderic acid S, ganodermanontriol and ganoderic acid TR were found to have the highest activities. A structure–activity relationship (SAR) analysis was performed. Extensive investigation of the SAR suggests the favorable structural features for the tubulin polymerization-stimulating activity of lanostane triterpenes. These findings would be helpful for further studies on the potential mechanisms of the anticancer activity of Ganoderma triterpenoids and give some indications on the design of tubulin-targeting anticancer agents.


Ganoderma Triterpenes Tubulin polymerization Microtubule Paclitaxel 



This paper is in memory of Mr. Ken Sawai, who always encouraged us to work with Ganoderma lingzhi. We also would like to express our gratitude to Mr. Takashi Sawai for providing some of the compounds used in this study. This work was supported by KAKENHI Grant Number 26660147.

Compliance with ethical standards

Conflict of interest

The authors have declared that there is no conflict of interest.


  1. 1.
    Cao Y, Wu S-H, Dai Y-C (2012) Species clarification of the prize medicinal Ganoderma mushroom “Lingzhi”. Fungal Divers 56:49–62. doi: 10.1007/s13225-012-0178-5 CrossRefGoogle Scholar
  2. 2.
    Smina TP, Mathew J, Janardhanan KK, Devasagayam TPA (2011) Antioxidant activity and toxicity profile of total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst occurring in South India. Environ Toxicol Pharmacol 32:438–446. doi: 10.1016/j.etap.2011.08.011 CrossRefPubMedGoogle Scholar
  3. 3.
    Sun J, He H, Bi JX (2004) Novel antioxidant peptides from fermented mushroom Ganoderma lucidum. J Agric Food Chem 52:6646–6652. doi: 10.1021/jf0495136 CrossRefPubMedGoogle Scholar
  4. 4.
    Zhu M, Chang Q, Wong LK et al (1999) Triterpene antioxidants from Ganoderma lucidum. Phytother Res 13:529–531CrossRefPubMedGoogle Scholar
  5. 5.
    Weng Y, Xiang L, Matsuura A et al (2010) Ganodermasides A and B, two novel anti-aging ergosterols from spores of a medicinal mushroom Ganoderma lucidum on yeast via UTH1 gene. Bioorg Med Chem 18:999–1002. doi: 10.1016/j.bmc.2009.12.070 CrossRefPubMedGoogle Scholar
  6. 6.
    Fatmawati S, Kurashiki K, Takeno S et al (2009) The inhibitory effect on aldose reductase by an extract of Ganoderma lucidum. Phytother Res 23:28–32. doi: 10.1002/ptr.2425 CrossRefPubMedGoogle Scholar
  7. 7.
    Guo L, Xie J, Ruan Y et al (2009) Characterization and immunostimulatory activity of a polysaccharide from the spores of Ganoderma lucidum. Int Immunopharmacol 9:1175–1182. doi: 10.1016/j.intimp.2009.06.005 CrossRefPubMedGoogle Scholar
  8. 8.
    Lin Z-B (2005) Cellular and molecular mechanisms of immuno-modulation by Ganoderma lucidum. J Pharmacol Sci 99:144–153. doi: 10.1254/jphs.CRJ05008X CrossRefPubMedGoogle Scholar
  9. 9.
    Liu J, Shimizu K, Kondo R (2010) The effects of ganoderma alcohols isolated from Ganoderma lucidum on the androgen receptor binding and the growth of LNCaP cells. Fitoterapia 81:1067–1072. doi: 10.1016/j.fitote.2010.06.029 CrossRefPubMedGoogle Scholar
  10. 10.
    Ríos J-L, Andújar I, Recio M-C, Giner R-M (2012) Lanostanoids from fungi: a group of potential anticancer compounds. J Nat Prod 75:2016–2044. doi: 10.1021/np300412h CrossRefPubMedGoogle Scholar
  11. 11.
    Lee J, Hung T (2009) Steroids and triterpenoid from the fruit bodies of Ganoderma lucidum and their cytotoxic activity. Nat Prod Sci 15:173–179Google Scholar
  12. 12.
    Wu T-S, Shi L-S, Kuo S-C (2001) Cytotoxicity of Ganoderma lucidum triterpenes. J Nat Prod 64:1121–1122. doi: 10.1021/np010115w CrossRefPubMedGoogle Scholar
  13. 13.
    Amen YM, Zhu Q, Tran H-B et al (2016) Lucidumol C, a new cytotoxic lanostanoid triterpene from Ganoderma lingzhi against human cancer cells. J Nat Med 70:661–666. doi: 10.1007/s11418-016-0976-2 CrossRefPubMedGoogle Scholar
  14. 14.
    Amen YM, Zhu Q, Afifi MS et al (2016) New cytotoxic lanostanoid triterpenes from Ganoderma lingzhi. Phytochem Lett. doi: 10.1016/j.phytol.2016.07.024 Google Scholar
  15. 15.
    Lee MK, Hung TM, Cuong TD et al (2011) Ergosta-7,22-diene-2β,3α,9α-triol from the fruit bodies of Ganoderma lucidum induces apoptosis in human myelocytic HL-60 cells. Phytother Res 25:1579–1585. doi: 10.1002/ptr.3447 CrossRefPubMedGoogle Scholar
  16. 16.
    Wang J-H, Zhou Y-J, Zhang M et al (2012) Active lipids of Ganoderma lucidum spores-induced apoptosis in human leukemia THP-1 cells via MAPK and PI3 K pathways. J Ethnopharmacol 139:582–589. doi: 10.1016/j.jep.2011.11.055 CrossRefPubMedGoogle Scholar
  17. 17.
    Chen N-H, Zhong J-J (2009) Ganoderic acid Me induces G1 arrest in wild-type p53 human tumor cells while G1/S transition arrest in p53-null cells. Process Biochem 44:928–933. doi: 10.1016/j.procbio.2009.03.018 CrossRefGoogle Scholar
  18. 18.
    Tang W, Liu J-W, Zhao W-M et al (2006) Ganoderic acid T from Ganoderma lucidum mycelia induces mitochondria mediated apoptosis in lung cancer cells. Life Sci 80:205–211. doi: 10.1016/j.lfs.2006.09.001 CrossRefPubMedGoogle Scholar
  19. 19.
    Wu G-S, Lu J-J, Guo J-J et al (2012) Ganoderic acid DM, a natural triterpenoid, induces DNA damage, G1 cell cycle arrest and apoptosis in human breast cancer cells. Fitoterapia 83:408–414. doi: 10.1016/j.fitote.2011.12.004 CrossRefPubMedGoogle Scholar
  20. 20.
    Weng C-J, Chau C-F, Hsieh Y-S et al (2008) Lucidenic acid inhibits PMA-induced invasion of human hepatoma cells through inactivating MAPK/ERK signal transduction pathway and reducing binding activities of NF-kappaB and AP-1. Carcinogenesis 29:147–156. doi: 10.1093/carcin/bgm261 CrossRefPubMedGoogle Scholar
  21. 21.
    Chang U-M, Li C-H, Lin L-I et al (2006) Ganoderiol F, a ganoderma triterpene, induces senescence in hepatoma HepG2 cells. Life Sci 79:1129–1139. doi: 10.1016/j.lfs.2006.03.027 CrossRefPubMedGoogle Scholar
  22. 22.
    Li C-H, Chen P-Y, Chang U-M et al (2005) Ganoderic acid X, a lanostanoid triterpene, inhibits topoisomerases and induces apoptosis of cancer cells. Life Sci 77:252–265. doi: 10.1016/j.lfs.2004.09.045 CrossRefPubMedGoogle Scholar
  23. 23.
    Liu J, Shimizu K, Tanaka A et al (2012) Target proteins of ganoderic acid DM provides clues to various pharmacological mechanisms. Sci Rep 2:905. doi: 10.1038/srep00905 PubMedPubMedCentralGoogle Scholar
  24. 24.
    Jordan MA, Wilson L (2004) Microtubules as a target for anticancer drugs. Nat Rev Cancer 4:253–265. doi: 10.1038/nrc1317 CrossRefPubMedGoogle Scholar
  25. 25.
    Cheng S, Sliva D (2015) Ganoderma lucidum for cancer treatment: we are close but still not there. Integr Cancer Ther. doi: 10.1177/1534735414568721 Google Scholar

Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan 2017

Authors and Affiliations

  1. 1.Division of Systematic Forest and Forest Products Sciences, Department of Agro-Environmental Sciences, Graduate School of Bioresource and Bioenvironmental SciencesKyushu UniversityFukuokaJapan
  2. 2.Faculty of Pharmaceutical SciencesKyushu UniversityFukuokaJapan
  3. 3.Department of Pharmacy, School of MedicineShenzhen UniversityShenzhenChina
  4. 4.Department of Pharmacognosy, Faculty of PharmacyMansoura UniversityMansouraEgypt

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