Download PDF
Planta Med 2005; 71(9): 819-824
DOI: 10.1055/s-2005-871249
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Immunomodulatory Activity and Influence on Mitotic Divisions of N-Benzoylphenylisoserinates of Lactarius Sesquiterpenoid Alcohols in vitro

Ewa Krawczyk1 , Mirosław Łuczak1 , Monika Kniotek2 , Anna Majewska1 , Dariusz Kawecki1 , Maria Nowaczyk2
  • 1Chair and Department of Medical Microbiology, Medical University of Warsaw, Warsaw, Poland
  • 2Department of Clinical Immunology, Transplantation Institute, Medical University of Warsaw, Warsaw, Poland
Further Information

Publication History

Received: November 20, 2004

Accepted: April 15, 2005

Publication Date:
29 July 2005 (online)

Also available at
    Permissions and Reprints

Abstract

Six N-benzoylphenylisoserinates of Lactarius sesquiterpenoid alcohols, which previously showed antiviral activities, were tested for their biological properties. Their influence on the mitotic division of the cells and on selected immunological parameters, e. g., T and B lymphocyte proliferation and synthesis of the cytokines: interleukin 2 (IL-2), tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) was assessed in vitro. All of the tested compounds significantly decreased the number of cell divisions. It appears that their influence on cellular divisions may be associated with anti-HSV activity. Moreover, one compound - isolactarorufin 8-epi-[N-benzoyl-(2′R,3′S)-3′-phenylisoserinate] significantly inhibited T lymphocyte proliferation and the synthesis of all tested cytokines.

Abbreviations

DMSO:dimethyl sulphoxide

FCS:foetal calf serum

HEPES:4-(2-hydroxyethyl)-1-piperazineethanesulphonic acid

MEM:minimum essential medium

PBMC:peripheral blood mononuclear cells

PBS:phosphate buffered saline

PHA:phytohaemagglutinin

PMA:phorbol myristate acetate

SAC:Staphylococcus aureus Cowan (strain)

Key words

Sesquiterpenes - taxol - Lactarius - mitotic divisions - lymphocyte proliferation - cytokines

References

  • 1 Daniewski W M, Vidari G. Constituents of Lactarius (Mushrooms). In: Herz W, Falk H, Kirby GW, Moore RE, Tamm C, editors Progress in the Chemistry of Organic Natural Products. Vol. 77 Springer-Verlag Wien, New York; 1999: pp 70-171
    Search in Google Scholar
  • 2 Muller W E, Dogovic N, Zahn R K, Maidhof A, Diehl-Seifert B, Becker C, Sachsse W, Gasic M J, Schroder H C. Inhibition of mitosis by avarol, a natural product isolated from the sponge Dysidea avara .  Basic Appl Histochem. 1985;  29 321-30
    PubMedSearch in Google Scholar
  • 3 Sheu J H, Hung K C, Wang G H, Duh C Y. New cytotoxic sesquiterpenes from the gorgonian Isis hippuris .  J Nat Prod. 2000;  63 1603-7
    CrossrefPubMedSearch in Google Scholar
  • 4 Tziveleka L A, Vagias C, Roussis V. Natural products with anti-HIV activity from marine organisms.  Curr Top Med Chem. 2003;  3 1512-35
    CrossrefPubMedSearch in Google Scholar
  • 5 Hoang V D, Tan G T, Zhang H J, Tamez P A, Hung N V, Cuong N M, Soejarto D D, Fong H H, Pezzuto J M. Natural anti-HIV agents - part I: (+)-demethoxyepiexcelin and verticillatol from Litsea verticillata .  Phytochemistry. 2002;  59 325-9
    CrossrefPubMedSearch in Google Scholar
  • 6 Hayashi K, Hayashi T, Ujita K, Takaishi Y. Characterisation of antiviral activity of a sesquiterpene, triptofordin C-2.  J Antimicrob Chemother. 1996;  37 759-68
    CrossrefPubMedSearch in Google Scholar
  • 7 Dolara P, Corte B, Ghelardini C, Pugliese A M, Cerbai E, Menichetti S, Lo Nostro A. Local anaesthetic, antibacterial and antifungal properties of sesquiterpenes from myrrh.  Planta Med. 2000;  66 356-8
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 Robles M, Aregullin M, West J, Rodriguez E. Recent studies on the zoopharmacognosy, pharmacology and neurotoxicology of sesquiterpene lactones.  Planta Med. 1995;  61 199-203
    Thieme ConnectPubMedSearch in Google Scholar
  • 9 Dirsch V M, Stuppner H, Vollmar A M. Cytotoxic sesquiterpene lactones mediate their death-inducing effect in leukemia T cells by triggering apoptosis.  Planta Med. 2001;  67 557-9
    Thieme ConnectPubMedSearch in Google Scholar
  • 10 Kim E J, Jin H K, Kim Y K, Lee H Y, Lee S Y, Lee K R, Zee O P, Han J W, Lee H W. Suppression by a sesquiterpene lactone from Carpesium divaricatum of inducible nitric oxide synthase by inhibiting nuclear factor-κB activation.  Biochem Pharmacol. 2001;  61 903-10
    CrossrefPubMedSearch in Google Scholar
  • 11 Duan H, Takaishi Y, Momota H, Ohmoto Y, Taki T, Jia Y, Li D. Immunosuppressive sesquiterpene alkaloids from Tripterygium wilfordii .  J Nat Prod. 2001;  64 582-7
    CrossrefPubMedSearch in Google Scholar
  • 12 Bottex-Gauthier C, Vidal D, Picot F, Potier P, Menichini F, Appendino G. In vitro biological activities of arglabin, a sesquiterpene lactone from the Chinese herb Artemisia myriantha Wall. (Asteraceae).  Biotechnol Ther. 1993;  4 77-98
    PubMedSearch in Google Scholar
  • 13 Zhao W, Ye Q, Tan X, Jiang H, Li X, Chen K, Kinghorn A D. Three new sesquiterpene glycosides from Dendrobium nobile with immunomodulatory activity.  J Nat Prod. 2001;  64 1196-200
    PubMedSearch in Google Scholar
  • 14 Daniewski W M, Gumulka M, Przesmycka D, Ptaszynska K, Bloszyk E, Drozdz B. Sesquiterpenes of Lactarius origin, antifeedant structure-activity relationships.  Phytochemistry. 1995;  38 1161-8
    PubMedSearch in Google Scholar
  • 15 Kobus M, Przybylski M, Daniewski W, Krawczyk E, Luczak M. Biological activities of sesquiterpenes of Lactarius origin [in Polish].  Probl Hig. 2001;  71 134-9
    PubMedSearch in Google Scholar
  • 16 Panchagnula R. Pharmaceutical aspects of paclitaxel.  Int J Pharm. 1998;  172 1-15
    CrossrefPubMedSearch in Google Scholar
  • 17 White C M, Martin B K, Lee L F, Haskill J S, Ting J P. Effects of paclitaxel on cytokine synthesis by unprimed human monocytes, T lymphocytes, and breast cancer cells.  Cancer Immunol Immunother. 1998;  46 104-12
    PubMedSearch in Google Scholar
  • 18 Tong A W, Seamour B, Lawson J M, Ordonez G, Vukelja S, Hyman W, Richards D, Stein L, Maples P B, Nemunaitis J. Cellular immune profile of patients with advanced cancer before and after taxane treatment.  Am J Clin Oncol. 2000;  23 463-72
    PubMedSearch in Google Scholar
  • 19 Kopczacki P, Gumulka M, Masnyk M, Grabarczyk H, Nowak G, Daniewski W M. Synthesis and antifeedant properties of N-benzoylphenylisoserinates of Lactarius sesquiterpenoid alcohols.  Phytochemistry. 2001;  58 775-87
    CrossrefPubMedSearch in Google Scholar
  • 20 Krawczyk E, Luczak M, Kobus M, Banka D, Daniewski W. Antiviral activity of N-benzoylphenylisoserinates of Lactarius sesquiterpenoid alcohols in vitro .  Planta Med. 2003;  69 552-4
    Thieme ConnectPubMedSearch in Google Scholar
  • 21 Topp K S, Meade L B, LaVail J H. Microtubule polarity in the peripheral processes of trigeminal ganglion cells: relevance for the retrograde transport of herpes simplex virus.  J Neurosci. 1994;  14 318-25
    PubMedSearch in Google Scholar
  • 22 Topp K S, Bisla K, Saks N D, LaVail J H. Centripetal transport of herpes simplex virus in human retinal pigment epithelial cells in vitro .  Neuroscience. 1996;  71 1133-44
    CrossrefPubMedSearch in Google Scholar
  • 23 Sodeik B, Ebersold M W, Helenius A. Microtubule-mediated transport of incoming herpes simplex virus 1 capsids to the nucleus.  J Cell Biol. 1997;  136 1007-21
    CrossrefPubMedSearch in Google Scholar
  • 24 Hammonds T R, Denyer S P, Jackson D E, Irving W L. Studies to show that with podophyllotoxin the early replicative stages of herpes simplex virus type 1 depend upon functional cytoplasmic microtubules.  J Med Microbiol. 1996;  45 167-72
    PubMedSearch in Google Scholar
  • 25 Norrild B, Lehto V P, Virtanen I. Organization of cytoskeleton elements during herpes simplex virus type 1 infection of human fibroblasts: an immunofluorescence study.  J Gen Virol. 1986;  67 97-105
    PubMedSearch in Google Scholar
  • 26 Wang J, Kobayashi M, Han M, Choi S, Takano M, Hashino S, Tanaka J, Kondoh T, Kawamura K, Hosokawa M. MyD88 is involved in the signalling pathway for taxol-induced apoptosis and TNF-α expression in human myelomonocytic cells.  Br J Haematol. 2002;  118 638-45
    CrossrefPubMedSearch in Google Scholar
  • 27 Cuthbert J A, Shay J W. Microtubules and lymphocyte responses: effect of colchicine and taxol on mitogen-induced human lymphocyte activation and proliferation.  J Cell Physiol. 1983;  116 127-34
    CrossrefPubMedSearch in Google Scholar

Ewa Krawczyk

Chair and Department of Medical Microbiology

Medical University of Warsaw

5 Chalubinski St.

02-004 Warsaw

Poland

Phone: +48-22-622-0028

Fax: +48-22-628-2739

Email: ewakrawczyk@gazeta.pl