Glucosinolates in crucifers and their potential effects

against cancer: Review

Gölge Sarıkamış
Ankara University, Faculty of Agriculture, Department of Horticulture, 06110, Dışkapı, Ankara, Turkey
(e-mail: golges@yahoo.com). Received 30 June 2008, accepted 15 April 2009.
Sarıkamış, G. 2009. Glucosinolates in crucifers and their potential effects against cancer: Review. Can. J. Plant Sci. 89: 953

959. There is growing interest in the health-promoting properties of cruciferous plant species, and people are urged to
incorporate these plants into their diet to fight cancer. Cruciferous vegetables contain glucosinolates, the precursors of
isothiocyanates, widely believed to protect humans against several forms of cancer. Iberin (1-isothiocyanato
3-
methylsulphinylpropane) and sulforaphane (1-isothiocyanato-4-methylsulphinylbutane) are two isothiocyanates most
Can. J. Plant Sci. Downloaded from cdnsciencepub.com by 86.127.208.44 on 04/24/23

abundant in broccoli that have been reported to protect against prostate, lung, breast and colon cancers. The aim of this
review is to provide updated information on the importance of glucosinolates and their breakdown products
(isothiocyanates) in delivering potential health benefits, and to describe the mechanism by which they act to provide
these beneficial effects. Factors influencing the glucosinolate content of cruciferous vegetables, both from genetic and
horticultural points of view, for future efforts to manipulate glucosinolate content of these vegetables are described.
Finally, a brief summary of recent developments concerning crucifer intake and cancer prevention is provided.

Key words: Brassica, crucifers, glucosinolates

Sarıkamış, G. 2009. Panorama des glucosinolates dans les crucifères et de leurs effets potentiels contre le cancer. Can. J. Plant
Sci. 89: 953
959. On s’intéresse de plus en plus aux propriétés médicinales des crucifères et encourage les gens à les inclure dans
leur alimentation pour combattre le cancer. En effet, les légumes de la famille des crucifères renferment des glucosinolates,
précurseurs des isothiocyanates, qu’on croit largement mettre l’être humain à l’abri de diverses formes de cancer. L’ibérine
(1-isothiocyanato
3-méthylsulphinylpropane) et le sulforaphane (1-isothiocyanato-4-méthylsulphinylbutane) en sont deux
des plus courants dans le brocoli. Ils assureraient, pense-t-on, une protection contre le cancer de la prostate, des poumons, du
sein et du côlon. Le présent article fait le point sur l’importance des glucosinolates et de leurs dérivés (isothiocyanates) pour la
santé et décrit le mécanisme par lequel ils procurent ces effets bénéfiques. Les facteurs qui influent sur la concentration de
glucosinolates dans les crucifères ont été examinés tant du point de vue de la génétique que de l’horticulture pour faciliter les
efforts déployés afin d’accroı̂tre la teneur en glucosinolates de ces légumes. Finalement, une courte récapitulation présente les
plus récents développements concernant l’absorption des crucifères et la prévention du cancer.

Mots clés: Brassica, crucifères, glucosinolates

There is growing interest among consumers in the 3-MSP), glucoraphanin (4-methylsulphinylbutyl, 4-

health benefits of foods, such as disease prevention. It
has long been known that diets rich in fruits and
vegetables protect humans against cancer. Cruciferous
vegetables, including broccoli, cabbage, cauliflower,
watercress and Brussels sprouts (Brassicaceae family),
are known to have potential health benefits due to the
presence of phytochemicals such as phenolics, vitamins,
minerals and sulphur-containing glycosides. Consump-
tion of these vegetables on a regular basis reduces the
risk of cancer (Zhao et al. 2001; Seow et al. 2002;
Fowke et al. 2003; Joseph et al. 2004; Wang et al. 2004;
Zickute et al. 2005; Moore et al. 2007; Traka et al.
2008). This is mainly attributed to the presence of
glucosinolates, a group of sulphur-containing secondary
plant metabolites, whose primary role in plants is
believed to be defence, protecting plants from herbi-
vores and stress. Although several different types of
glucosinolates exist, depending on their chemical struc-
tures, aliphatics and indoles are more frequent. Among
aliphatics, glucoiberin (3-methylsulphinylpropyl,
953
MSB), sinigrin (2-propenyl), progoitrin (2-hydroxy
3-
butenyl), and indoles, glucobrassicin (3-indolylmethyl),
neoglucobrassicin (1-methoxy
3-indolylmethyl), 4-
methoxy-glucobrassicin (4-methoxy
3-indolylmethyl),
and 4-hydroxy-glucobrassicin (4-hydroxy
3-indolyl-
methyl) are mostly present in cruciferous vegetables
(Fig. 1). The cancer-preventing property of crucifers is
most likely due to the activity of 3-MSP isothiocya-
nates, commonly known as iberin (1-isothiocyanato
3-
methylsulphinylpropane), and 4-MSB isothiocyanate,
commonly known as sulforaphane (1-isothiocyanato-4-
methylsulphinylbutane), derived, respectively, from 3-
MSP and 4-MSB glucosinolates by the action of the
Abbreviations: ESP, epithiospecifier protein;
GSTM1, glutathione S-transferase M1; 3-MSP, 3-
methylsulphinylpropyl; 4-MSB, 4-methylsulphinyl-
butyl, QTL, quantitative trait loci
 954 CANADIAN JOURNAL OF PLANT SCIENCE

Chemical structure Chemical name Common name

3-Methylsulphinylpropyl Glucoiberin
S Glucose
CH3 SO CH2 C
3 NOSO3

S Glucose
4-Methylsulphinylbutyl Glucoraphanin
CH3 SO CH2 C
4 NOSO3

2-Propenyl Sinigrin
S Glucose
C H2 CH [CH 2] C
NOSO 3
2-Hydroxy–3-butenyl Progoitrin
S Gl
C H2 CHC H CH2 C
NOSO 3
OH
3-Indolylmethyl Glucobrassicin
S Glucose
Can. J. Plant Sci. Downloaded from cdnsciencepub.com by 86.127.208.44 on 04/24/23

CH2 C
NOSO 3

H
4-Hydroxy–3-indolylmethyl 4-Hyrdoxy-
OH glucobrassicin
S Glucose
CH2 C
NOSO3

H
4-Methoxy–3-indolylmethyl 4-Methoxy-
OC H3 glucobrassicin
S Glucose
C H2 C
NOSO3

H
1-Methoxy–3-indolylmethyl Neoglucobrassicin
S Glucose
CH2 C
NOSO3

OC H3

Fig. 1. Chemical structure of some prominent glucosinolates found in cruciferous vegetables.

endogenous myrosinase activated as a result of tissue
damage in plants (Fig. 2).
While acting as a defence system for plants, these
metabolites also deliver protection for humans, most
importantly against cancer. In addition to iberin and
sulforaphane, the metabolites derived from the corre-
sponding aliphatic glucosinolates that have been best
described, other bioactive compounds, such as 3,3-
di-indolylmethane, derived from indole glucosinolates
(Fig. 3), have also been associated with such activity
(Nachshon-Kedmi et al. 2004). However, less informa-
tion is available on the role of indole compounds
compared with aliphatic glucosinolate derivatives.
The anti-cancer properties of cruciferous vegetables
have led researchers to explore this important quality, as
well as the factors influencing the glucosinolate content
of this specific group of plants, to enable future efforts
for improved health benefits. The aim of the current
review is to provide updated information about recent
developments regarding glucosinolates and their break-
down products from a horticultural point of view.
Factors Influencing the Glucosinolate Content
of Brassicas
Glucosinolates are generally classified as aliphatics,
indoles and aromatics. When this variation is combined
with their intriguing biosynthetic pathways, the diffi-
culty in identifying factors influencing glucosinolate
production are clear. However, identifying these factors
may play a key role in manipulating the glucosinolate
profile and content of individual plants in order to
derive new plants with desired glucosinolate production.
 SARIKAMIŞ * EFFECTS OF GLUCOSINOLATES AGAINST CANCER 955

Glucoraphanin
4-MSB Glucosinolate
S Glucose
CH3 SO CH2 C
4 NOSO3

CH 3 SO CH 2 N C S CH 3 SO CH 2 C N
4 4
Sulforaphane Sulforaphane Nitrile
4-MSB Isothiocyanate 4-MSB Nitrile

S Glucose
CH 3 SO CH2 C
3 NOSO3
Glucoiberin
3-MSP Glucosinolate
Can. J. Plant Sci. Downloaded from cdnsciencepub.com by 86.127.208.44 on 04/24/23

CH 3 SO CH 2 N C S CH 3 SO CH 2 C N
3 3
Iberin Iberin Nitrile
3-MSP Isothiocyanate 3-MSP Nitrile

Fig. 2. Conversion of 4-MSB and 3-MSP glucosinolates to the corresponding isothiocyanates (sulforaphane and iberin) and nitriles
(sulforaphane nitrile and iberin nitrile) via myrosinase activity.

Among these factors, genetic background is one of the
major determinants, especially when aliphatics are
considered. Broccoli, synthesizing the most prominent
aliphatics, has been studied extensively to elucidate the
influence of genetics on aliphatic glucosinolate produc-
tion. These studies were initially aimed at the develop-
ment of new improved cultivars with enhanced
glucosinolate content, eventually providing an insight
into the genetic determinants of this trait (Mithen et al.
2003). The introgression of genomic segments from
Brassica villosa, a wild Brassica, to a commercial
broccoli not only led the development of high-glucosi-
nolate broccoli (Mithen et al. 2003; Sarıkamış et al.
2006), but also helped reveal the effect of introgressing
wild genomic segments on the glucosinolate content of
broccoli, while explaining the effect and interaction of
quantitative trait loci (QTL) linked with glucosinolate
biosynthesis in broccoli. Furthermore, markers asso-
ciated with these QTLs were described using genetic and
molecular approaches (Mithen et al. 2003; Sarıkamış
et al. 2006). These studies revealed that the presence of a
single B. villosa allele at a QTL designated as QTL-1
resulted in a two- to threefold increase in glucosinolates,
and affected the ratio of 3-MSP to 4-MSB. When
B. villosa alleles were present at QTL-1, the predominant
glucosinolate was 3-MSP. On the other hand, B. villosa
alleles at QTL-2 altered the ratio of 3-MSP and 4-MSB,
but not the overall levels of methylsulphinylalkyl
glucosinolates (Sarıkamış et al. 2006). These findings
are important first steps that may guide future breeding
efforts aimed at the development of cultivars with added
health benefits.
Soil fertility and environmental factors during the
growth of plants are associated with the amount of
glucosinolates produced, rather than the type of gluco-
sinolate synthesized. Studies conducted to explore the
relationship between the mineral content of soil and
glucosinolate levels of plants suggest that the mineral
content of soil influences glucosinolate levels (Zhao
et al. 1994; Mithen et al. 2003). Total glucosinolate and

Indolyl-3-acetonitrile

CH2 C N

N
S Glucose R
CH2 C CH2
NOSO3
- Myrosinase CH2 OH
N N
N
N R R
R R

Indolyl glucosinolate Indolyl-3-carbinol

3,3-diindolylmethane

Fig. 3. Conversion of indole glucosinolates to indolyl compounds such as indolyl
3-acetonitrile and indolyl
3-carbinol, that is
further metabolized to 3,3-diindolylmethane.
 956 CANADIAN JOURNAL OF PLANT SCIENCE
glucobrassicin concentrations in cabbages were reported
to be maximized with supplementary applications of low
levels of nitrogen and high levels of sulphur (Rosen et al.
2005), resulting in the accumulation of aliphatic and
aromatic glucosinolates, in contrast to the applications
of high nitrogen doses, which affected glucosinolates
with indolyl side chains (Chen et al. 2006; Li et al. 2007).
This is mainly attributed to the existence of the sulphur
ion in the aliphatic molecule and the presence of the
nitrogen ion in the indole molecule, being influenced by
external applications boosting the corresponding gluco-
sinolates. In addition to the two major elements, a
micronutrient, selenium, was also shown to alter gluco-
sinolate content in a positive manner to a certain extent
Can. J. Plant Sci. Downloaded from cdnsciencepub.com by 86.127.208.44 on 04/24/23
in broccoli. However, enhanced applications over a
certain dose were shown to reduce the amount of
glucosinolates produced (Robbins et al. 2005).
Fewer studies demonstrate the effect of environmental
conditions and the possible stress factors associated with
them on glucosinolate content. Higher temperatures
during cultivation were shown to positively influence
glucosinolate concentrations in broccoli seedlings
(Pereira et al. 2002; Shonhof et al. 2006). An experiment
demonstrating the effect of growing Brassica species
(kale and cabbage) in two different seasons (spring and
fall sowing) revealed that the highest total glucosinolate
content was obtained when harvest was at high tem-
peratures and long day length, while aliphatics were
higher during fall and indoles were higher in spring
(Cartea et al. 2008; Velasco et al. 2007). Detailed studies
on the effects of ecology on glucosinolate content may
allow the utilization of cultural practices to alter the
glucosinolate levels of crucifers.
The evaluation of the effects of storage, processing
and cooking on glucosinolate content of broccoli,
Brussels sprouts, cauliflower and cabbage suggests that
storage in a refrigerator for 7 days had no significant
effect, and caused only a small loss in glucosinolate
content (Song and Thornalley 2007). Fine chopping of
vegetables was reported to result in a significant
decrease in glucosinolate content (Song and Thornalley
2007), which might be caused by myrosinase being
activated as a result of chopping consequently degrading
glucosinolates.
The effect of different cooking methods showed that
while steaming and stir-frying did not cause a major loss
in glucosinolate content, boiling in water caused im-
portant losses and microwaving was found to slightly
decrease glucosinolate content (Rungapamestry et al.
2006). Processes such as blanching, boiling and steaming
were shown to significantly influence total glucosino-
lates in cauliflower, but steaming was shown to influence
to a relatively lesser extent (Volden et al. 2009). Cooking
Brassica vegetables for shorter durations is important
for improved health benefits (Lopez-Berenguer et al.
2007). The changes in the glucosinolate content of
crucifers occurring during processing and cooking may
all be associated with the myrosinase activity induced by
these factors, probably resulting in the degradation of
glucosinolates. As a result, the glucosinolate content is
decreased. Further estimations of the amount of gluco-
sinolate degradation products followed by these treat-
ments may provide a better understanding of the
mechanism.
Factors Influencing the Sulforaphane Yield of the
Precursor Glucosinolate
Identifying factors influencing sulforaphane yield of the
precursor glucosinolate is also important in determining
the beneficial effects of crucifers. The mechanism of the
conversion of glucosinolates into the corresponding
breakdown products was briefly mentioned above
(Figs. 2 and 3). The conversion (hydrolysis) is initiated
by myrosinase coming into contact with glucosinolates
upon damage in plant tissues, resulting in the cleavage of
the thio-glucose bond of the molecule forming the
unstable thiohydroxymate-O-sulphonate in aliphatics,
consequently forming an array of breakdown products
depending on the structure of the precursor glucosino-
late (Fig. 2). Among the array of products obtained as a
result of the hydrolysis of aliphatic glucosinolates,
isothiocyanates have been reported to possess potential
health benefits, but nitriles have not been reported to
possess any such benefits so far. This being the case, the
mechanism diverting the unstable intermediate into the
breakdown products has been of interest. Although
detailed biochemical and genetic evidence is limited, a
number of studies demonstrate that a heat-sensitive
protein named epithiospecifier protein (ESP) is respon-
sible for the conversion of glucosinolates into nitriles
(Fig. 2) (Bernardi et al. 2000; Matusheski et al. 2004;
Zabala et al. 2005; Burow et al. 2008). Epithiospecifier
protein is a small protein purified from B. napus
(Bernardi et al. 2000). Initial studies demonstrated that
this protein interacts with the unstable intermediate
product (thiohydroxymate-O-sulphonate). Genetic stu-
dies identified a major QTL affecting nitrile/isothiocya-
nate formation in Arabidopsis, which was very close to a
gene encoding a homologue of a B. napus ESP (Lambrix
et al. 2001). By cloning a protein with ESP activity and
sequence homology to the ESP of Arabidopsis thaliana,
scientists demonstrated that ESP activity led hydrolysis
of glucoraphanin (precursor of sulforaphane) to form
sulforaphane nitrile, instead of sulforaphane, revealing a
negative association between ESP activity and forma-
tion of sulforaphane (Matusheski et al. 2006). The
findings of a recent study suggest that ESP is not only
responsible for the conversion of aliphatic glucosinolates
to the corresponding compounds, but also acts together
with myrosinase to control nitrile production from
indole glucosinolates as well as Arabidopsis (Burow
et al. 2008). The study has demonstrated that the ESP
locus formerly known to control the production of
nitrile from aliphatics is also critical for indole-3-
acetonitrile formation from 3-indolylmethyl glucosino-
lates (Fig. 3) together with Epithiospecifier modifier 1
 SARIKAMIŞ * EFFECTS OF GLUCOSINOLATES AGAINST CANCER
(ESM1) gene in Arabidopsis, an important finding that
provided a further insight to the entire mechanism of
this conversion.
Crucifer Intake and Prevention of Cancer
Physiological and epidemiological studies have demon-
strated that inclusion of cruciferous vegetables in
the diet is associated with significantly reduced risk of
breast (Fowke et al. 2003) stomach and colorectal
(Seow et al. 2002; Hara et al. 2003; Zickute et al.
2005), kidney (Moore et al. 2007), bladder (Munday
et al. 2008) and prostate cancers (Traka et al. 2008).
The protective effect of crucifers is likely due to the
activity of isothiocyanates. Initial studies on isothiocya-
Can. J. Plant Sci. Downloaded from cdnsciencepub.com by 86.127.208.44 on 04/24/23
nates focused on the ability of isothiocyanates to induce
phase 2 detoxification enzymes such as quinone reduc-
tase, glutathione-S-transferases and UDP-glucuronosyl
transferases (Fahey et al. 1997) via ARE-mediated
transcription. Among isothiocyanates, sulforaphane
has been shown to be a potent inducer of phase 2
detoxification enzymes in cell culture and animal tests
(Fahey et al. 1997). Initially, it was believed that
sulforaphane protected cells through Nrf-2 mediated
induction of phase 2 enzymes enhancing cell defence
against oxidative damage leading the removal of poten-
tial carcinogens from metabolism (Dinkova-Kostova
et al. 2002). Recent studies suggest that sulforaphane
provides protection via a complex array of mechanisms
by inhibiting carcinogen activating enzymes, enhancing
carcinogen detoxifying enzymes and inducing cell cycle
arrest and apoptosis as described recently by Juge et al.
(2007). In general, it has been shown that upon
absorption, sulforaphane is conjugated with glutathi
one and metabolised via the mercapturic acid pathway
and excreted mainly as N-acetylcysteine conjugates
(Conaway et al. 2000).
Sulforaphane has been reported to be effective in
initiation and progression of a range of tumors in
animal models. Several studies demonstrated that sul-
foraphane helped develop significantly fewer and smal-
ler intestinal polyps in ApcMin/ mice, prevented
mouse skin tumorigenesis at initial stages, helped
suppress the growth of T24 bladder cancer cells and
suppressed the invasiveness of human breast cancer cells
in vitro (Rose et al. 2005; Gills et al. 2006; Hu et al.
2006; Shan et al. 2006). Increased cabbage intake was
reported to prevent or delay the metastatic and invasive
capacity of breast cancer cells in operable breast cancer
patients (Altundağ et al. 2006).
The genetic background of individuals is also im-
portant in understanding the association between diet
and protection from cancer (Törüner et al. 2001; Wang
et al. 2004; Moore et al. 2007). Cruciferous vegetables
are revealed to reduce the risk of cancer in people with a
glutathione S-transferase M1 (GSTM1) allele. Although
three major mammalian GST gene families exist,
GSTM1-1 and glutathione S-transferase P1-1 (GSTP1-
1) possess the greatest activity on sulforaphane (Meyer
957
et al. 1995). Epidemiological evidence suggests that
people with at least one functional GSTM-1 allele gain
better protection than people with homozygous deletion
of GSTM-1 (Joseph et al. 2004). Wang et al. (2004)
reported that higher cruciferous vegetable intake re-
duced lung cancer risk only among individuals with
GSTM1-present genotype. Similarly, in a population-
based case-control study of prostate cancer risk, it was
shown that men with GSTM1-present genotype and
high broccoli intake had the greatest reduction in risk
(Joseph et al. 2004). A recent dietary intervention study
focusing on the analysis of global gene expression
profiles in the human prostate gland has demonstrated
the influence of GSTM1 genotype in protection against
cancer. Individuals with at least one GSTM1 allele
benefit more than those with a GSTM1 null genotype
who excrete a higher amount of sulforaphane available
in the metabolism after broccoli consumption via
mercapturic acid pathway (Traka et al. 2008).
In light of this evidence, it can be concluded that
cruciferous vegetables, broccoli in particular, are sources
of important phytochemicals, and may help protect
against several forms of cancers when eaten on a regular
basis. However, although glucosinolates offer health-
promoting properties, the amount of glucosinolates in
commercial cultivars is low, and the mechanism by
which people can benefit from the available glucosino-
lates is complicated. It is suggested to increase the
available levels of glucosinolates in plants, evaluate ways
to further divert the conversion of glucosinolates into
the beneficial isothiocyanates, and to identify the
mechanistic basis of the protective effects of crucifers,
especially on specific tissues and their interaction with
genotype. The current review gathers information re-
garding these major stages, demonstrating factors hav-
ing an impact on these crucial steps for added health
benefits.
Altundağ, K., Gündeşlioğlu, O. and Altundağ, O. 2006.
Increased cabbage intake may inhibit metastatic and invasive
capacity of breast cancer cells by inhibiting CXCL12 (SDF-1
alpha)/CXCR4. Med. Hypotheses 66: 672.
Bernardi, R., Negri, A., Ronchi, S. and Palmieri, S. 2000.
Isolation of the epithiospecifier protein from oil-rape (Brassica
napus spp. oleifera) seed and its characterisation. FEBS Lett.
467: 296
298.
Burow, M., Zang, Z-Y., Ober, J. A., Lambrix, V. M.,
Wittstock, U., Gershenzon, J. and Kliebenstein D. J. 2008.
ESP and ESM1 mediate indol
3-acetonitrile production from
indol
3-ylmethyl glucosinolate in Arabidopsis. Phytochemis-
try 69: 663
671.
Cartea, M. E., Velasco, P., Obregon, S., Padilla, G. and De
Haro, A. 2008. Seasonal variation in glucosinolate content in
Brassica oleracea crops grown in northwestern Spain. Phyto-
chemistry 69: 403
410.
Chen, X., Zhu, Z., Ni, X. and Qian, Q. 2006. Effect of nitrogen
and sulphur supply on glucosinolates in Brassica campestris
ssp. chinensis. Agric. Sci. China. 5: 603
608.
 958 CANADIAN JOURNAL OF PLANT SCIENCE
Conaway, C. C., Getahun, S. M., Liebes, L. L., Pusateri, D. J.,
Topham, D. K., Botero-Omary, M. and Chung, F. L. 2000.
Disposition of glucosinolates and sulforaphane in humans
after ingestion of steamed and fresh broccoli. Nutr. Cancer 38:
168
178.
Dinkova-Kostova, A. T., Holtzclaw, W. D., Cole, R. N., Itoh,
K., Wakabayashi, N., Katoh, Y., Yamamoto, M. and Talalay,
P. 2002. Direct evidence that sulfhydryl groups of keap1 are
the sensors regulating induction of phase 2 enzymes that
protect against carcinogens and oxidants. Proc. Natl. Acad.
Sci. 99: 11908
11913.
Fahey, J. W., Zhang, Y. and Talalay, P. 1997. Broccoli sprouts:
An exceptionally rich source of inducers of enzymes that
protect against chemical carcinogens. Proc. Nat. Acad. Sci. 94:
10367
10372.
Can. J. Plant Sci. Downloaded from cdnsciencepub.com by 86.127.208.44 on 04/24/23
Fowke, J. H., Chung, F. L., Jin, F., Qi, D., Cai, Q., Conaway,
C., Cheng, J. R., Shu, X-O., Gao, Y-T. and Zheng, W. 2003.
Urinary isothiocyanate levels, Brassica, and human breast
cancer. Cancer Res. 63: 3980
3986.
Gills, J. J., Jeffery, E. H., Matusheski, N. V., Moon, R. C.,
Lantvit, D. D. and Pezzuto, J. M. 2006. Sulforaphane prevents
mouse skin tumorigenesis during the stage of promotion.
Cancer Lett. 236: 72
79.
Hara, M., Hanaoka, T., Kobayashi, M., Otani, T., Adachi, H.
Y., Montani, A., Natsukawa, S., Shaura, K., Koizumi, Y.,
Kasuga, Y., Matsuzawa, T., Ikekawa, T., Sasaki, S. and
Tsugane, S. 2003. Cruciferous vegetables, mushrooms, and
gastrointestinal cancer risks in a multicenter, hospital-based
case-control study in Japan. Nutr. Cancer 46: 138
147.
Hu, R., Khor, T. O., Shen, G., Jeong, W. S., Hebbar, V., Chen,
C., Xu, C., Reddy, B., Chada, K. and Kong, A. N. 2006. Cancer
chemoprevention of intestinal polyposis in ApcMin/ mice by
sulforaphane, a natural product derived from cruciferous
vegetable. Carcinogenesis 27: 2038
2046.
Joseph, M. A., Moysich, K. B., Freudenheim, J. L., Shields, P.
G., Bowman, E. D., Zhang, Y., Marshall, J. R. and Ambrosone,
C. B. 2004. Cruciferous vegetables, genetic polymorphisms in
glutathione S-transferases M1 and T1, and prostate cancer
risk. Nutr. Cancer 50: 206
213.
Juge, N., Mithen, R. F. and Traka, M. 2007. Molecular basis
for chemoprevention by sulforaphane: a comprehensive re-
view. Cell. Mol. Life Sci. 64: 1105
1127.
Lambrix, V., Reichelt, M., Mitchell-Olds, T., Kliebenstein,
D. J. and Gershenzon, J. 2001. The Arabidopsis epithiospecifier
protein promotes the hydrolysis of glucosinolates to nitriles
and influences Trichoplusia ni herbivory. Plant Cell 13: 2793

2807.
Li, S., Schonhof, I., Krumbein, A., Li, L., Stützel, H. and
Schreiner, M. 2007. Glucosinolate concentration in Turnip
(Brassica rapa ssp. rapifera L.) roots as affected by nitrogen
and sulfur supply. J. Agric. Food Chem. 55: 8452
8457.
Lopez-Berenguer, C., Carvajal, M., Moreno, D. A. and Viguera,
A. C. G. 2007. Effects of microwave cooking conditions on
bioactive compounds present in Broccoli inflorescences. J.
Agric. Food Chem. 55: 10001
10007.
Matusheski, N. V., Swarup, R., Juvik, J. A., Mithen, R.,
Bennett, M. and Jeffery, E. H. 2006. Epithiospecifier protein
from broccoli (Brassica oleracea L. ssp. italica) inhibits
formation of the anticancer agent sulforaphane J. Agric.
Food Chem. 54: 2069
2076.
Matusheski, N. V., Juvik, J. A. and Jeffrey, E. H. 2004.
Heating decreases epithiospecifier protein activity and
increases sulforaphane formation in broccoli. Phytochemistry
265: 1273
1281.
Meyer, D. J., Crease, D. J. and Ketterer, B. 1995. Forward and
reverse catalysis and product sequestration by human glu-
tathione S-transferases in the reaction of GSH with dietary
aralkyl isothiocyanates. Biochem. J. 306: 565
569.
Mithen, R., Faulkner, K., Magrath, R., Rose, P., Williamson,
G. and Marquez, J. 2003. Development of isothiocyanate-
enriched broccoli, and its enhanced ability to induce phase 2
detoxification enzymes in mammalian cells. Theor. Appl.
Genet. 106: 727
734.
Moore, L. E., Brennan, P., Karami, S., Hung, R. J., Hsu, C.,
Boffetta, P., Toro, J., Zaridze, D., Janout, V., Bencko, V.,
Navratilova, M., Szeszenia-Dabrowska, N., Mates, D., Mukeria
Holcatova, I., Welch, R., Chanock, S., Rothman, N. and Chow,
W. H. 2007. Glutathione S-transferase polymorphisms, cruci-
ferous vegetable intake and cancer risk in the Central and
Eastern European Kidney Cancer Study. Carcinogenesis 28:
1960
1964.
Munday, R., Mhawech-Fauceglia, P., Munday, C. M.,
Paonessa, J. D., Tang, L., Munday, J. S., Lister, C., Wilson,
P., Fahey, J. W., Davis, W. and Zhang, Y. 2008. Inhibition of
urinary bladder carcinogenesis by broccoli sprouts. Cancer
Res. 68:1593
1600.
Nachshon-Kedmi, M., Fares, F. A. and Yannai, S. 2004.
Induction of apoptosis in human prostate cancer cell line,
PC3, by 3?3?-diindolylmethane through the mitochondrial
pathway. Prostate 61: 153
160.
Pereira, F. M., Rosa, E., Fahey, J. W., Stephenson, K. K.,
Carvalho, R. and Aires, A. 2002. Influence of temperature and
ontogeny on the levels of glucosinolates in broccoli (Brassica
oleracea var. italica) sprouts and their effect on the induction
of mammalian phase 2 enzymes. J. Agric. Food Chem. 50:
6239
6244.
Robbins, R. J., Keck, A. S., Banuelos, G. and Finley, J. W.
2005. Cultivation conditions and selenium fertilization alter
the phenolic profile, glucosinolate, and sulforaphane content
of broccoli. J. Med. Food 8: 204
214.
Rose, P., Huang, O., Ong, C. N. and Whiteman, M. 2005.
Broccoli and watercress suppress matrix metalloproteinase-9
activity and invasiveness of human MDA-MB-231 breast
cancer cells. Toxicol. Appl. Pharmacol. 209: 105
113.
Rosen, C. J., Fritz, V. A., Gardner, G. M., Hecht, S. S.,
Carmella, S. G. and Kenney, P. M. 2005. Cabbage yield and
glucosinolate concentrations as affected by nitrogen and
sulphur fertility. HortScience 40: 1493
1498.
Rungapamestry, V., Duncan, A. J. Fuller, Z. and Ratcliffe, B.
2006. Changes in glucosinolate concentrations, myrosinase
activity, and production of metabolites of glucosinolates in
cabbage (Brassica oleracea var. capitata) cooked for different
durations. J. Agric. Food Chem. 54: 7628
7634.
Sarıkamış, G., Marquez, J., Maccormack, A., Bennett, R.,
Roberts, J. and Mithen, R. 2006. High glucosinolate broccoli-
A delivery system for sulforaphane. Mol. Breed. 18: 219
228.
Seow, A., Yuan, J. M., Sun, C. L., Van Den Berg, D., Lee, H.
P. and Yu, M. C. 2002. Dietary isothiocyanates, glutathione S-
transferase polymorphisms and colorectal cancer risk in the
Singapore Chinese Health Study. Carcinogenesis 23: 2055

2061.
Shan, Y., Sun, C., Zhao, X., Wu, K., Cassidy, A. and Bao, Y.
2006. Effect of sulforaphane on cell growth, G0/G1 phase cell
progression and apoptosis in human bladder cancer T24 cells.
Int. J. Oncol. 29: 883
888.
 SARIKAMIŞ * EFFECTS OF GLUCOSINOLATES AGAINST CANCER
Shonhof, I., Kläring, H. F., Krumbein, A., Claußen, W. and
Schreiner, M. 2006. Effect of temperature increase under low
radiation conditions on phytochemicals and ascorbic acid in
greenhouse grown broccoli. Agric. Ecosyst. Environ. 119:
103
111.
Song, L. and Thornalley, P. J. 2007. Effect of storage,
processing and cooking on glucosinolate content of Brassica
vegetables. Food Chem. Toxicol. 45: 216
224.
Törüner, G. A., Akyerli, C., Ucar, A., AkI, T., Atsu, N., Özen,
H., Tez, M., Çetinkaya M. and Özçelik, T. 2001. Polymorph-
isms of glutathione S-transferase genes (GSTM1, GSTP1 and
GSTT1) and bladder cancer susceptibility in the Turkish
population. Arch. Toxicol. 75: 459
464.
Traka, M., Gasper, A. V., Melchini A., Bacon, J. R., Needs, P.
W., Frost, V., Chantry, A., Jones, A. M. E, Ortori, C. A.,
Barrett, D. A., Ball, R. Y., Mills, R. D. and Mithen, R. F. 2008.
Can. J. Plant Sci. Downloaded from cdnsciencepub.com by 86.127.208.44 on 04/24/23
Broccoli consumption interacts with GSTM1 to perturb
oncogenic signalling pathways in the prostate. PLoS ONE 3:
e2568
Velasco, P., Cartea, M. E., Gonzalez, C., Vilar, M. and Ordas,
A. 2007. Factors affecting the glucosinolate content of kale
(Brassica oleracea acephala Group). J. Agric. Food Chem. 55:
955
962.
Volden, J., Borge, G. I. A., Hansen, M., Wicklund, T.
and Bengtsson, G. B. 2009. Processing (blanching, boiling,
steaming) effects on the content of glucosinolates and
959
antioxidant-related parameters in cauliflower (Brassica oler-
acea L. ssp. botrytis). Food Sci. Technol. 42: 63
73.
Wang, L. I., Giovannucci, E. L., Hunter, D., Neuberg, D., Su,
L. and Christiani, D. C. 2004. Dietary intake of Cruciferous
vegetables, Glutathione S-transferase (GST) polymorphisms
and lung cancer risk in a Caucasian population. Cancer Causes
Control 10: 977
985.
Zabala, M. D. T., Grant, M., Bones, A. M., Bennett, R., Yin, S.
L., Kissen, R. and Rossiter, J. T. 2005. Characterisation of
recombinant epithiospecifier protein and its over-expression in
Arabidopsis thaliana. Phytochemistry 66: 859
867.
Zhao, B., Seow, A., Lee, A. J., Poh, W. T., The, M., Eng, P.,
Wang, Y. T., Tan, W. C., Yu, M. C. and Lee, H. P. 2001.
Dietary isothiocyanates, glutathione S-transferase-M1, -T1
polymorphisms and lung cancer risk among Chinese woman
in Singapore. Cancer Epidem. Biomarkers Prevent. 10:
1063
1067.
Zhao, F. J., Evans, E. J., Bilsborrow, P. E. and Syers, J. K.
1994. Influence of nitrogen and sulfur on the glucosinolate
profile of rape-seed (Brassica napus L.). J. Sci. Food Agric. 64:
295
304.
Zickute, J., Strumylaite, L., Dregyal, L., Petrauskiene, J.,
Dudzevicius, J. and Strartilovas, E. 2005. Vegetables and fruits
and risk of stomach cancer. Medicina (Kaunas, Lithiuania) 41:
733
740.