Planta Med 2003; 69(1): 15-20
DOI: 10.1055/s-2003-37030
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Cancer Chemopreventive in vitro Activities of Isoflavones Isolated from Iris germanica

Eckhard Wollenweber1 , Jan Frederik Stevens2 , 4 , Karin Klimo3 , Jutta Knauft3 , Norbert Frank3 , Clarissa Gerhäuser3
  • 1Institut für Botanik, Technische Universität, Darmstadt, Germany
  • 2Department of Chemistry, Oregon State University, Corvallis, OR, USA
  • 3AG Chemoprävention (C0202), Deutsches Krebsforschungszentrum, Heidelberg, Germany
  • 4Present address: Institut für Pflanzenbiochemie, Halle/Saale, Germany
Further Information

Publication History

Received: May 3, 2002

Accepted: August 13, 2002

Publication Date:
04 February 2003 (online)

Abstract

Six known isoflavones were isolated from the rhizomes of Iris germanica, and were established by UV, MS and NMR techniques as irisolidone (1), irisolidone 7-O-α-D-glucoside (1a), irigenin (2), irilone (3), iriflogenin (4), and iriskashmirianin (5). These compounds were examined for their cancer chemopreventive potential. They were shown to be potent inhibitors of cytochrome P450 1A activity with IC50 values in the range 0.25 - 4.9 μM. The isoflavones 2, 3 and 5 displayed moderate activity as inducers of NAD(P)H:quinone reductase (QR) in cultured mouse Hepa 1c1c7 cells, with CD values (concentration required to double the specific activity of QR) of 3.5 - 16.7 μM, whereas weak activity was observed with compounds 4 and 5 in the radical (DPPH) scavenging bioassay (IC50 values 89.6 and 120.3 μM, respectively). With respect to anti-tumor promoting potential based on anti-inflammatory mechanisms, none of the compounds demonstrated significant activity in the concentration range tested.

Abbreviations

APCI:atmospheric pressure chemical ionization

CD:concentration required for doubling of the specific activity of NAD(P)H:quinone reductase

Cox:cyclooxygenase

Cyp:cytochrome P450

DAD:diode-array detector

DPPH:1,1-diphenyl-2-picrylhydrazyl

HMBC:heteronuclear multiple bond correlation

IC50:half-maximal inhibitory concentration

iNOS:inducible nitric oxide synthase

NF:naphthoflavone

QR:NAD(P)H:quinone reductase

SC50:half-maximal scavenging concentration

References

  • 1 Steinegger E, Hänsel R. Lehrbuch der Pharmakognosie und Phytopharmazie. 4. Ed Springer-Verlag 1988: 252
  • 2 Uphof J CTh. Dictionary of economic Plants. 2.Ed./Reprint. Lehre. Verlag von J Cramer 1968: 284
  • 3 Sporn M B, Dunlop N M, Newton D L, Smith J M. Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs. Fed.  Proc.. 1976;  35 1332-8
  • 4 Theisen C. Chemoprevention: What’s in a name? J. Natl.  Cancer Inst.. 2001;  93 743
  • 5 Steele V E, Boone C W, Lubet R A, Crowell J A, Holmes C A, Sigman C C. et al . Preclinical drug development paradigms for chemopreventives. Hematol./Oncol. Clin.  North Am.. 1998;  12 943-61, v-vi
  • 6 Alberts D S, Garcia D J. An overview of clinical cancer chemoprevention studies with emphasis on positive phase III studies. J.  Nutr.. 1995;  125 (Suppl) 692S-7S
  • 7 Crespi C L, Miller V P, Penman B W. Microtiter plate assays for inhibition of human, drug-metabolizing cytochromes P450. Anal.  Biochem.. 1997;  248 188-90
  • 8 Gerhäuser C, Klimo K, Heiss E, Neumann I, Gamal Eldeen A, Knauft J. et al .Mechanism-based in vitro screening of potential cancer chemopreventive agents. Mutat. Res. 2002;: (in press)
  • 9 Smith P K, Krohn R I, Hermanson G T, Mallia A K, Gartner F H, Provenzano M D. et al . Measurement of protein using bicinchoninic acid. Anal.  Biochem.. 1985;  150 76-85
  • 10 Gerhäuser C, You M, Liu J, Moriarty R M, Hawthorne M, Mehta R G. et al . Cancer chemopreventive potential of sulforamate, a novel analogue of sulforaphane that induces phase 2 drug-metabolizing enzymes.  Cancer Res.. 1997;  57 272-8
  • 11 van Amsterdam F T, Roveri A, Maiorino M, Ratti E, Ursini F. Lacidipine: a dihydropyridine calcium antagonist with antioxidant activity. Free Radic. Biol.  Med.. 1992;  12 183-7
  • 12 Jang M, Cai L, Udeani G O, Slowing K V, Thomas C F, Beecher C W. et al . Cancer chemopreventive activity of resveratrol, a natural product derived from grapes.  Science. 1997;  275 218-20
  • 13 Heiss E, Herhaus C, Klimo K, Bartsch H, Gerhauser C. Nuclear factor-κB is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms. J. Biol.  Chem.. 2001;  276 32 008-15
  • 14 Arisawa M, Morita N, Kondo Y, Takemoto T. Studies on constituents of Iris genus plants. IV. The constituents of Iris florentina L. (2). Chem. Pharm.  Bull.. 1973;  21 2323-28
  • 15 Kachroo P K, Razdan T K, Qurishi M A, Khuroo M A, Koul S, Dhar K L. Two isoflavones from Iris kashmiriana .  Phytochemistry. 1990;  29 1014-16
  • 16 Al-Khalil S, Al-Eisawi D, Kato M, Iinuma M. New isoflavones from Iris nigricans. J. Nat.  Prod.. 1994;  57 201-5
  • 17 Al-Khalil S, Al-Eisawi D. The chemotaxonomic profile of Iris atrofusca and I. atropurpurea. Bull. Fac. Pharm.  (Cairo Univ.). 1995;  33 (special issue) 111-4
  • 18 Aburjai T, Amro , Al-Khalil S, Al-Eisawi D. The chemical constituents of Iris petrana .  Acta Technologiae et Legis Medicamenti. 2000;  11 137-45
  • 19 Dewick P M. Isoflavonoids. In: Harborne JB, editor The Flavonoids - Advances in Research since 1986. London; Chapman and Hall 1994: 117-238
  • 20 Pailer M, Franke F. Über Inhaltsstoffe der Iris germanica (Schwertlilie). Monatsh.  Chem.. 1973;  104 1394-408
  • 21 Ali A A, El-Emary N A, El-Moghazi M -A, Darwish F M, Frahm A W. Three isoflavonoids from Iris germanica .  Phytochemistry. 1983;  22 2061-63
  • 22 Kelloff G J, Crowell J A, Hawk E T, Steele V E, Lubet R A, Boone C W. et al . Strategy and planning for chemopreventive drug development: clinical development plans II: Genistein. J. Cell.  Biochem., Suppl.. 1996;  26 114-26
  • 23 Ohshima H, Bartsch H. Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis. Mutat.  Res.. 1994;  305 253-64

Prof. Dr. E. Wollenweber

Institut für Botanik

Technische Universität Darmstadt

Schnittspahnstr. 4

D-64287 Darmstadt

Germany

Email: wollenweber@bio.tu-darmstadt.de

Fax: +49 6151 16 4630