Skip to main content

Advertisement

SpringerLink
Log in

Fungal substances as modulators of NF-κB activation pathway

  • Original Paper
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

MCF7 breast cancer cell line, carrying a luciferase reporter gene under the control of nuclear factor kappa B (NF-κB)-responsive promoter, was established and used for the screening of fungal organic extracts for their ability to interfere with the NF-κB activation pathway. Twenty-eight crude fungal extracts, out of 242, were found to inhibit NF-κB reporter activity by more than 40%. Furthermore, positive extracts were used to evaluate their antiproliferative activity as well as their ability to influence the phosphorylation and degradation levels of IκBa. Fungal extracts prepared from Marasmius oreades and Cyathus striatus showed significant inhibitory effects on the NF-κB activation pathway. Taken together, our results support the notion of the presence of novel activities that might be utilized as cancer therapeutics.

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
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

CL:

culture liquid

DEE:

diethyl ether

DMSO:

dimethyl sulfoxide

EAC:

ethyl acetate

EAL:

ethyl alcohol

FCS:

fetal calf serum

IκB:

inhibitory protein kappa B

NF-κB:

nuclear factor kappa B

TNF-α:

tumor necrosis factor-α

References

  1. Wasser SP, Weis AL (1999) Medicinal properties of substances occurring in higher Basidiomycetes mushrooms: current perspectives (Review). Int J Med Mushr 1:31–62

    CAS  Google Scholar 

  2. Wasser SP, Weis AL (1999) Therapeutic effects of substances occurring in higher Basidiomycetes mushrooms: a modern perspective. Crit Rev Immunol 19:65–96

    PubMed  CAS  Google Scholar 

  3. Zaidman B, Yassin M, Mahajna J, Wasser SP (2005) Medicinal mushroom modulators of molecular targets as cancer therapeutics. Appl Microbiol Biotechnol 67(4):453–468

    Article  PubMed  CAS  Google Scholar 

  4. Smith JE, Rowan NJ, Sullivan R (2002) Medicinal mushrooms: their therapeutic properties and current medical usage with special emphasis on cancer treatments. Cancer Research UK. University of Strathclyde, Glasgow

    Google Scholar 

  5. McMoris TC, Anchel MJ (1963) The structures of the basidiomycete metabolites illudin S and illudin M. J Am Chem Soc 85:831

    Article  Google Scholar 

  6. McMoris TC, Yu J, Lira R, Dawe R, McDonald JR, Waters SJ, Estes LA, Kelner MJ (2001) Structure–activity studies of antitumor agent irofulven (hydroxymethylacylfulvene) and analogues. J Org Chem 66:6158–6163

    Article  CAS  Google Scholar 

  7. Dick RA, Yu X, Kensler TW (2004) NADPH alkenal/one oxidoreductase activity determines sensitivity of cancer cells to the chemotherapeutic alkylating agent irofulven. Clin Cancer Res 10(4):1492–1499

    Article  PubMed  CAS  Google Scholar 

  8. Jong SC, Donovick R (1989) Antitumor and antiviral substances from fungi. Adv Appl Microbiol 34:183–262

    Article  PubMed  CAS  Google Scholar 

  9. Wolf-Reiner A (2001) Bioactive sesquiterpenes produced by fungi: are they useful for humans as well? Curr Med Chem 8:583–606

    Google Scholar 

  10. Dembitsky VM, Rezanka T, Spizek J, Hanus LO (2005) Secondary metabolites of slime molds (myxomycetes). Phytochemistry 66:747–769

    Article  PubMed  CAS  Google Scholar 

  11. Lorenzen K, Anke T (1998) Basidiomycetes as a source for new bioactive natural products. Curr Org Chem 2:329–364

    CAS  Google Scholar 

  12. Smania A Jr, Monache FD, Smania EFA, Cuneo RS (1999) Antibacterial activity of steroidal compounds isolated from Ganoderma applanatum (Pers.) Pat. (Aphyllophoromycetidae) fruit body. Int J Med Mushr 1:325–330

    Google Scholar 

  13. Smania EFA, Monache FD, Smania A Jr, Yunes RA, Cuneo RS (2003) Antifungal activity of sterols and triterpenes isolated from Ganoderma annulare. Fitoterapia 74:375–377

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  15. Sliva D (2003) Ganoderma lucidum (reishi) in cancer treatment. Inegr Cancer Ther 2(4):358–364

    Article  Google Scholar 

  16. Lindequist U, Niedermeyer THJ, Julich WD (2005) The pharmacological potential of mushrooms. eCAM 2(3):285–299

    PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  18. Nakshatri H, Bhat-Nakshatri P, Martin DA, Goulet RJ Jr, Sledge GW Jr (1997) Constitutive activation of NF-κB during progression of breast cancer to hormone-independent growth. Mol Cell Biol 17:3629–3639

    PubMed  CAS  Google Scholar 

  19. Pahl H (1999) Activators and target genes of Rel/NF-κB transcription factors. Oncogene 18:6853–6866

    Article  PubMed  CAS  Google Scholar 

  20. Zandi E, Karin M (1999) Bridging the gap: composition, regulation, and physiological function of the IκB kinase complex. Mol Cell Biol 19:4547–4551

    PubMed  CAS  Google Scholar 

  21. Karin M, Ben-Neriah Y (2000) Phosphorylation meets ubiquitination: the control of NF-[k]B activity. Ann Rev Immunol 18:621–663

    Article  CAS  Google Scholar 

  22. Karin M, Cao Y, Greten FR, Li ZW (2002) NF-κB in cancer: from innocent bystander to major culprit. Nat Rev Cancer 2:301–310

    Article  PubMed  CAS  Google Scholar 

  23. Petrova RD, Wasser SP, Mahajna JA, Denchev CM, Nevo E (2005) Potential role of medicinal mushrooms in breast cancer treatment: current knowledge and future perspectives. Int J Med Mushr 7(1):141–156

    Article  CAS  Google Scholar 

  24. Petrova RD, Wasser SP, Mahajna JA, Denchev CM, Nevo E (2005) Medicinal mushrooms: a new source for breast cancer therapeutics. Int J Med Mushr 7(2–3):445–446

    Google Scholar 

  25. Mattila P, Könkö K, Eurola M, Pihlava J-M, Astola J, Vahteristo L, Hietaniemi V, Kumpulainen J, Valtonen M, Piironen V (2001) Contents of vitamins, mineral elements, and some phenolic compounds in cultivated mushrooms. J Agric Food Chem 49:2343–2348

    Article  PubMed  CAS  Google Scholar 

  26. Nakamura T, Akiyama Y, Matsugo S, Uzuka Y, Shibata K, Kawagishi H (2003) Purification of caffeic acid as an antioxidant from submerged culture mycelia of Phellinus linteus (Berk. et Curt.) Teng (Aphyllophoromycetidae). Int J Med Mushr 5:163–167

    Article  CAS  Google Scholar 

  27. Park YM, Kim IT, Park HJ, Choi JW, Park KY, Lee JD, Nam BH, Kim DG, Lee JY, Lee KT (2004) Anti-inflammatory and anti-nociceptive effects of the methanol extract of Fomes fomentarius. Biol Pharm Bull 27(10):1588–1593

    Article  PubMed  CAS  Google Scholar 

  28. Kis Z, Closse A, Sigg HP, Hruban L, Snatzke G (1970) Die struktur von panepoxydon und verwandten pilzmetaboliten. Helv Chim Acta 53(7):1577–1597

    Article  CAS  Google Scholar 

  29. Erkel G, Anke T, Sterner O (1996) Inhibition of NF-κB activation by panepoxydone. Biochem Biophys Res Commun 226:214–221

    Article  PubMed  CAS  Google Scholar 

  30. Yassin M, Mahajna JA, Wasser SP (2003) Submerged cultured mycelium extracts of higher Basidiomycetes mushrooms selectively inhibit proliferation and induce differentiation of K562 human chronic myelogenous leukemia cells. Int J Med Mushr 5:261–276

    Article  Google Scholar 

  31. Khan IA, Alam SS, Jabbar A (2001) Standardization of medium for the production of maximum phytotoxic activity by Fusarium oxysporum f. sp. ciceris. Pakistan J Biol Sci 4(11):1374–1376

    Article  Google Scholar 

  32. Talwar GP (1974) Handbook of practical immunology. National Book Trust, New Delhi

    Google Scholar 

  33. Bar-Shai M, Reznick AZ (2006) Peroxynitrite induces an alternative NF-κB activation pathway in L8 rat myoblasts. Antioxid Redox Signal 8:639–652

    Article  PubMed  CAS  Google Scholar 

  34. Karin M, Greten FR (2005) NF-κB: linking inflammation and immunity to cancer development and progression. Nat Rev 5:749–759

    Article  CAS  Google Scholar 

  35. Aggarwal BB, Sethi G, Nair A, Ichikawa H (2006) Nuclear factor-κB: a holy grail in cancer prevention and therapy. Curr Sign Transd Ther 1:25–52

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  37. Watabe M, Hishikawa K, Takayanagi A, Shimizu N, Nakaki T (2004) Caffeic acid phenetyl ester induces apoptosis by inhibition of NF-κB and activation of Fas in human breast cancer MCF-7 cells. J Biol Chem 279(7):6017–6026

    Article  PubMed  CAS  Google Scholar 

  38. Lu Q-Y, Sartippour MR, Brooks MN, Zhang Q, Hardy M, Go VL, Li FP, Heber D (2004) Ganoderma lucidum spore extract inhibits endothelial and breast cancer cells in vitro. Oncol Rep 12:659–662

    PubMed  Google Scholar 

  39. Tomasi S, Lohezic-Le DF, Sauleau P, Bezivin C, Boustie J (2004) Cytotoxic activity of methanol extracts from Basidiomycete mushrooms on murine cancer cell lines. Pharmazie 59(4):290–293

    PubMed  CAS  Google Scholar 

  40. Tateno H, Goldstein IJ (2004) Partial identification of carbohydrate-binding sites of a Galalpha1,3Galbeta1,4GlcNAc-specific lectin from the mushroom Marasmius oreades by site-directed mutagenesis. Arch Biochem Biophys 427(1):101–109

    Article  PubMed  CAS  Google Scholar 

  41. Warner RL, Winter HC, Speyer CL, Varani J, Oldstein IJ, Murphy HS, Johnson KJ (2004) Marasmius oreades lectin induces renal thrombotic microangiopathic lesions. Exp Mol Pathol 77(2):77–84

    Article  PubMed  CAS  Google Scholar 

  42. Davies DG, Hodge P (2005) Biosynthesis of the allene (−)-marasin in Marasmius ramealis. Org Biomol Chem 3:1690–1693

    Article  PubMed  CAS  Google Scholar 

  43. Tobe Y, Yamashita D, Takahashi T, Inata M, Sato J, Kakiuchi K, Kobiro K, Odaira Y (1990) Synthesis of (±)-marasmic acid via 1-oxaspirohexane rearrangement. J Am Chem Soc 112:775–779

    Article  CAS  Google Scholar 

  44. Anke T, Kupka J, Shramm G, Steglich W (1980) Antibiotics from basidiomycetes. X. Scorodonin, a new antibacterial and antifungal metabolite from Marasmius scorodonius (Fr.). Fr J Antibiot (Tokyo) 33(5):463–467

    CAS  Google Scholar 

  45. Allbutt AD, Ayer WA, Brodie HJ, Johri BN, Taube H (1970) Cyathin, a new antibiotic complex produced by Cyathus helenae. Can J Microbiol 17:1401–1407

    Article  Google Scholar 

  46. Anke T, Oberwinkler F, Steglich W, Höfle G (1976) The striatins—new antibiotics from the basidiomycete Cyathus striatus (Huds. ex Pers.). Wild J Antibiot 30(3):221–225

    Google Scholar 

  47. Ayer WA, Paice MG (1976) Metabolites of the Bird’s Nest Fungi. Part 4. The isolation and structure determination of cybullol, a metabolite of Cyathus bulleri Brodie. Can J Chem 54:910–916

    Article  CAS  Google Scholar 

  48. Ayer WA, McCaskill RH (1981) The cybrodins, a new class of sesquiterpenes. Can J Chem 59(14):2150–2158

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. J. Duyster, Department of Internal Medicine III, Technical University of Munich, Munich, Germany, for providing the Baf3/p185 Bcr-Abl cell line. We also thank Novartis Pharmaceuticals, Basel, Switzerland, for providing the Imatinib mesylate (Gleevec). We thank Mrs. Robin Permut for the English editing of the paper. This research was partly supported by the Ministry of Science and Technology of Israel, Grant No. alona5246 to J.M.

Author information

Authors and Affiliations

  1. International Center for Cryptogamic Plants and Fungi, Institute of Evolution, University of Haifa, Mt. Carmel, Haifa, Israel

    Roumyana D. Petrova, Solomon P. Wasser & Eviatar Nevo

  2. Migal-Galilee Technology Center, South Industrial Zone, Kiryat Shmona, Israel

    Roumyana D. Petrova & Jamal Mahajna

  3. Faculty of Medicine, Technion, Haifa, Israel

    Roumyana D. Petrova & Abraham Z. Reznick

  4. Institute of Life Science and Natural Resources, Korea University, Seoul, Korea

    Cvetomir M. Denchev

Authors
  1. Roumyana D. Petrova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jamal Mahajna
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abraham Z. Reznick
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Solomon P. Wasser
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cvetomir M. Denchev
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eviatar Nevo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roumyana D. Petrova.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Petrova, R.D., Mahajna, J., Reznick, A.Z. et al. Fungal substances as modulators of NF-κB activation pathway. Mol Biol Rep 34, 145–154 (2007). https://doi.org/10.1007/s11033-006-9027-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-006-9027-5

Keywords

Search

Navigation