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Can thiocyanate and thiocyanate precursors from
Brassica species support the tumor therapy?
W.-D. Jülich, U. Lindequist
Institute of Pharmacy, Department of Pharmaceutical Biology, Ernst- Moritz- Arndt- University Greifswald
F.-L.- Jahn -Straße 15, 17487 Greifswald, Germany
Conclusions
Thiocyanates activate the metabolism of cells. This effect together with the well known immune stimulating effect could support
prophylaxis and therapy of cancer diseases. After a vegetable rich nutrition with a high glucosinolate or thiocyanate content the
thiocyanate level in the blood is increased. Although this increase is only small in comparison to the strong increase of thiocyanate level
in tumor patients the demonstrated cellular effects let expect considerable benefit for the patient. Possible interactions
with the tumor therapy have to be observed carefully.
Introduction
Cancer prevention by food is well investigated and supported
by many authors. It was shown that an extract of broccoli
sprouts (Brassica oleracea, convar. botrytis, var. italica) is a
highly promising substance for bladder cancer prevention.
During urinary excretion the compounds from the extract are
selectively delivered to the bladder epithelium [1]. Also
Sauerkraut, which is prepared from slightly fermented
cabbage, exhibits in animal studies a promising tumor
inhibiting potential [2]. Brassicaceae are especially rich in
glucosinolates (“organic thiocyanates”) [3]. Besides
glucosinolates, the plants contain enzymes, which are able to
break down the glucosinolates mainly into isothiocyanates
and thiocyanates (“anorganic thiocyanate” SCN-) [4].
Therefore Brassica spec. contain high amounts of SCN(Tab. 1). To complete the cancer prevention, anorganic
thiocyanate is therefore of special interest.
Tab. 1: SCN- content of Brassica spec.[5]
Brassica spec.
Var.
SCNµmol/kg
B. oleracea L.
var. capitata
con. var. alba
con. var. rubra
var. botrytis
var. sabouda
var. gemnifera
334-1500
400-800
500-2000
1300-2170
217-2500
var. gongylodes
var. rapa
350-700
1500-2500
B. rapa L.
Serum thiocyanate level of humans
Normal conditions
Brassica rich nutrition
 60-70 % of the SCN--pool is endogen produced.
 Under normal nutrition conditions people take up
about 50 µmol SCN´- per day.
 This together with the endogen produced amount
results in a serum thiocyanate level of about 50-70
µmol/l.
Tumor patients
Tumors of
The thiocyanate level of patients with malignant tumors
is much higher than those in health people [6]. In
average the SCN--level is about two times higher than in
the controls (Table 2). This can be evaluated as sign of
an increased activity of the immune system of the
patient.
n
Sceleton system
Gastrointestinal system
Mamma
Female genital system
Thoracic cavity
Skin
Controls
A nutrition with a high Brassica content could
support the SCN--uptake.
The thiocyanate level in serum is increased after
brassica rich nutrition by about 1-10 µmol/l [7].
13
µmol
SCN-/l
175+78
68
25
39
60
89
294
150+68
147+92
139+47
125+53
100+7
63+41
Influence of an increased thiocyanate level on cell metabolism
Methods
Results
We have investigated the influence of SCN- on
the metabolism of human cells (FL-cells). An
essential precondition to control the metabolism
of cells over longer times is to realize their
survival under in vivo like conditions. These
conditions can be realized in a perfused cell
culture [8]. Fresh nutrition medium is supplied
and
metabolic
products
are
removed
continuously. During 12 days a very stable
glucose consumption as parameter for cell
metabolism and vitality can be measured.
The metabolism of the cells is
activated. The glucose consumption
is
significantly
(Friedman-test)
increased. The cells are more stable
against stress.
-50
-60
guinea pig, female
mice, female
N
SC
clo
ph
osp
ha
mid
+
-40
Cy
N
-30
clo
ph
osp
ha
mid
-20
tro
l
-10
Cy
 But in another animal model, the teratogenic effects of
procarbazins on Os metacarpale III, Ossa digitalia III and V and
the Fibula are increased by application of SCN- [10].
0
SC
 This side effect of a tumor chemotherapy with cyclophosphamid
is decreased by application of SCN- in an animal model [9].
10
con
 The number of leucocytes is decreased during the treatment with
cyclophosphamid.
number of leucocytes (%)
Influence of SCN- on side effects of tumor therapy
guinea pig, male
mice, male
References:
[1] R. Munday, P.Mhawech-Fauceglia, Ch. M. Munday, J.D. Paonessa, L Tang, J. S. Munday, C. Lister, P Wilson, J. W. Fahey, W. Davis and Y. Zhang: Inhibition of Urinary Bladder Carcinogenesis by Broccoli Sprouts. Cancer Res. 68, 1593–600 (2008).
[2] E.-L. Ryhanen: J.Agric. Food Chem 50, 6798-6803 (2002).
[3] M.E. Daxenbichler, C.H. Vanstetten, P.H. Williams.: Glucosinolate Products in Commercial Sauerkraut. J. Agric. Food Chem. 28, 809-811 (1980).
[4] J.W. Fahey, Y. Zhang, P.Talalay.: Broccoli spouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc. Natl. Acad. Sci. USA 94, 10367-10372 (1997).
[5] W. Weuffen, H. Decker: Thiocyanat –ein bioaktives Ion. IS.M.H. Verlag Törpin 2004.
[6] W.-D. Jülich, W. Weuffen, H.-L. Jenssen und H. Köhler: Beziehungen zwischen den Ergebnissen des Makrophagen-Elektrophorese-Mobilitäts-Tests und dem Rhodanidspiegel bei Patienten mit malignen Tumoren, Autoaggressionskrankheiten und nach Transplantation. Acta biol. med. german. 34, 1541 – 1547 (1975).
[7] W,.D.Jülich, A. Kramer, V. Hingst, H.-G. Sonntag, C, Schütt, M. Daut, A. Schulz, G. Bahlmann, H. Zöllner, R. Hampel, E. Panzig: Untersuchungen zur Stimulierung der Immunantwort bei der Hepatitis-B-Schutzimpfung durch eine alimentäre Thiocyanatsupplementierung bei gesunden Probanden und bei Dialysepatienten. Umweltmed.
Forsch. Prax 2, 71-83 (1997).
[8] T h. v.Woedtke, U. Lindequist, N. Alhitari, C. Kusnick, W.-D. Jülich, P. Abel: The usefulness of a biosensor controlled perfusion cell culture for the investigation of new drugs demonstrated with the marine fungus Kirschsteinothelia maritima. Pharmazie 57 (4)270 (2002)
[9] A. Kramer, M. Kühn, W.-D. Jülich: Verminderung der durch Cyclophosphamid induzierten Leukopoesesuppression durch Thiocyanat. Hyg. Med. 21, 34 (1996).
[10]S.Liefländer: Zum Einfluss von Folsäure und Thiozyanat auf die Knochenreifung der LEW.1A-Ratte unter Procarbazinapplikation in zytostatischer Dosierung. Diss. Med. Fak. Univ. Greifswald 2006