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Marasmius oreades substances block NF-κB activity through interference with IKK activation pathway

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Abstract

The activation pathway of nuclear transcription factor kappa B (NF-κB) is a key mechanism for the progression of carcinogenesis at the molecular level. NF-κB is related to the promotion of cell proliferation, inhibition of apoptosis, and the enhancement of tumor metastasis and angiogenesis. Marasmius oreades culture liquid extract, which was previously shown to affect NF-κB activation through inhibition of the phosphorylation of the inhibitory protein kappa B (IκBα), was subjected to liquid chromatography in order to investigate the specific mechanism of action of the active moieties present in the extract. Four fractions were obtained and tested for their abilities to block NF-κB activation pathway at different molecular levels. All fractions showed an anti-proliferative potential with no apparent cytotoxicity on MCF7 breast cancer cell line. Two out of the four fractions strongly affected the phosphorylation of IκBα and the NF-κB reporter activity in MCF7 breast cancer cell line. In addition, these two fractions prevented the p65 nuclear translocation and seemed to interfere with the IκB kinase (IKK) activation pathway. The IKK pathway is a major cellular signaling pathway set at a crossroad leading to NF-κB activation by a variety of stimuli. Also, these two fractions induced apoptosis of MCF7 cells. This study adds additional valuable data to our knowledge on the anticancer potential of fungal metabolites. It is the first report showing the medicinal value of M. oreades as a natural source of low-molecular-weight bioactive substances able to affect the process of tumorogenesis through the direct blockage of NF-κB activation at the IKK level.

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Abbreviations

COX:

Cyclooxigenase

IκBα:

Inhibitory protein kappa B

IKK:

IκB kinase complex

NF-κB:

Nuclear factor kappa B

TNF-α:

Tumor necrosis factor α

References

  1. Aggarwal BB (2004) Nuclear factor-κB: the enemy within. Cancer Cell 6:203–208

    Article  PubMed  CAS  Google Scholar 

  2. 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 

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

    Article  PubMed  CAS  Google Scholar 

  4. Manson MM, Holloway KA, Howells LM, Hudson EA, Plummer SM, Squires MS, Prigent SA (2000) Modulation of signal-transduction pathways by chemopreventive agents. Chemoprotection 28(2):7–12

    CAS  Google Scholar 

  5. 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 

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

    CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  8. Halpern GM, Miller AH (2002) Medicinal mushrooms. Ancient remedies for modern ailments. M. Evans and Company Inc., New York

    Google Scholar 

  9. 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 

  10. 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 

  11. 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 

  12. 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 

  13. 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 

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

    CAS  Google Scholar 

  15. Anke T, Kupka J, Schramm 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 

  16. 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 

  17. Davies DG, Hodge P (2005) Biosynthesis of the allene (−)-marasin in Marasmius ramealis. Org Biomol Chem 3(9):1690–1693

    Article  PubMed  CAS  Google Scholar 

  18. Petrova RD, Mahajna J, Reznick AZ, Wasser SP, Denchev CM, Nevo E (2007) Fungal substances as modulators of NF-κB activation pathway. Mol Biol Rep 34(3):145–154

    Article  PubMed  CAS  Google Scholar 

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

    Google Scholar 

  20. Bar-Shai M, Reznick AZ (2006) Peroxynitrite induces an alternative NF-κB activation pathway in L8 rat myoblasts. Antioxid Redox Signal 8(3–4):639–652

    Article  PubMed  CAS  Google Scholar 

  21. Zaidman BZ, Wasser SP, Nevo E, Wasser J (2007a) Androgen receptor-dependent and -independent mechanisms mediate Ganoderma lucidum activities in LNCaP prostate cancer cells. Int J Oncol 31(4):959–967

    PubMed  CAS  Google Scholar 

  22. Zaidman BZ, Wasser SP, Nevo E, Mahajna J (2007b) Coprinus comatus and Ganoderma lucidum interfere with androgen receptor function in LNCaP prostate cancer cells. Mol Biol Rep (in press)

  23. Garg A, Aggarwal BB (2002) Nuclear transcription factor-κB as a target for cancer drug development. Leukemia 16:1053–1068

    Article  PubMed  CAS  Google Scholar 

  24. Debatin KM (2004) Apoptosis pathways in cancer and cancer therapy. Cancer Immunol Immunother 53:153–159

    Article  PubMed  Google Scholar 

  25. Park YM, Won JH, Kim YH, Choi JW, Park HJ, Lee KT (2005) In vivo and in vitro anti-inflammatory and anti-nociceptive effects of the methanol extract of Inonotus obliquus. J Ethnopharmacol 101:120–128

    Article  PubMed  Google Scholar 

  26. Hsieh T, Wu P, Park S, Wu JM (2006) Induction of cell cycle changes and modulation of apoptogenic/anti-apoptotic and extracellular signaling regulatory protein expression by water extracts of I’m-Yunity™ (PSP). BMC Compl Alt Med 1–15

  27. Korsmeyer SJ (1999) BCL-2 gene family and the regulation of programmed cell death. Cancer Res 59:1693s–1700s

    PubMed  CAS  Google Scholar 

  28. Ramachandran C, You W (1999) Differential sensitivity of human mammary epithelial and breast carcinoma cell lines to curcumin. Breast Cancer Res Treat 54(3):269–278

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

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. 3–998, to JM and by the Krol Foundation of Barnegat NJ USA, to AZR.

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Authors and Affiliations

  1. International Center for Cryptogamic Plants and Fungi, Institute of Evolution, University of Haifa, Mt. Carmel, Haifa, 31905, Israel

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

  2. Migal-Galilee Technology Center, Cancer Drug Discovery Program, P.O. Box 831, Kiryat Shmona, Israel

    Roumyana D. Petrova, Jamal Mahajna, Nili Ruimi & Sherbel Sussan

  3. Department of Anatomy and Cell Biology, Faculty of Medicine, Technion, Haifa, Israel

    Roumyana D. Petrova & Abraham Z. Reznick

  4. Institute of Botany, Bulgarian Academy of Sciences, 23 Acad. G. Bonchev St., 1113, Sofia, Bulgaria

    Cvetomir M. Denchev

Authors
  1. Roumyana D. Petrova
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  2. Jamal Mahajna
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  3. Solomon P. Wasser
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  4. Nili Ruimi
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  5. Cvetomir M. Denchev
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  6. Sherbel Sussan
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  7. Eviatar Nevo
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  8. Abraham Z. Reznick
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Correspondence to Abraham Z. Reznick.

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Petrova, R.D., Mahajna, J., Wasser, S.P. et al. Marasmius oreades substances block NF-κB activity through interference with IKK activation pathway. Mol Biol Rep 36, 737–744 (2009). https://doi.org/10.1007/s11033-008-9237-0

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  • DOI: https://doi.org/10.1007/s11033-008-9237-0

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