Slide 1



Cecha charakterystyczną roślin krzyżowych jest
duża zawartość

Glukozynolanów



Glukozynolany

i produkty ich rozpadu izotiocyjany

maja dobrze udokumentowane działanie
przeciwnowotworowe. Konsumpcja tych warzyw
zmniejsza ryzyko wielu typów nowotworów.

Glukozynolany



Glukozynolany

są prekursorami

izotiocyjanów

(mustard oils).



odgrywają ważną role u roślin:



Allelopathy



Hamują wzrost innych roślin w pobliżu



Szerokie działanie podobne do antybiotyków



takie jak przeciw pasożytom roślinnym
(nematocidal) przeciwbakteryjne, przeciwgrzybicze
antiprotozoal agent - środek przeciw pierwotniakom i
przeciw insektom.



Około 120 glukozynolanów
zidentyfikowano w roślinach .



Większość glukozynolanów
wyizolowano z roślin kapustowatych
jednakże istnieje około 15 rodzaj
roślin, które również zawierają
glukozynolany.



Niektórzy ludzie mogą konsumować
około 300 mg/d (~660 µmol/d),
jednakże brak jest szerokich badan na
ten temat.

Glukozynolany

Dietary cancer chemopreventive compounds

Resveratrol

Grape and red wine
Vinca vinifera

(-)Epigallocatechin-3-O-gallate
EGCG

Green tea
Camellia sinensis, Theaceae

Lycopene

Tomato
Lycopersicon esculente, Solanaceae

Quercitrin

Blueberry
Vaccinium myrtillus,
Ericaceae

Daidzein

Soya beans
Glycine max, Leguminosae

Coumestrol

Soya beans
Glycine max, Leguminosae

Curcumin

Turmeric
Curcuma domestica, Zingiberaceae

Genistein

Soya beans
Glycine max, Leguminosae

Folate

Vitamin K

Sulforaphane

Broccoli, Brasica oleracea
Cruciferae

Glucobrassicin

Horseradish
Armoracia rusticana, Cruciferae

Indole-3-carbinol

Cruciferous vegetables
Cruciferae

Sinalbin

White mustard
Sinapis alba, Cruciferae

Sinigrin

Black mustard
Brassica nigra, Cruciferae

Silymarin

Milk thistle,
Silybum marianum, Compositae

Glukozynolany : jako prekursorzy
aktywnych biologicznie związków

N O

glukorafanin
a

ITC

Izotiocyjaniany

Merozynaz
a

N O SO

C S

Glukorafanina

Sulforafan

Glukozynolany rozpadają się do ITC
kiedy roślina jest miażdżona lub żuta

Indole-3-carbinol



Indole-3-carbinol
(I3C)



Występuje w
roślinach
kapustowatych



Indukuje CYP1A1



Hamuje FMO1



Flavin containing
monooxygenase 1

Katchamart, et al. Concurrent flavin-containing monooxygenase down-regulation and cytochrome p-450 induction by dietary
indoles in rat: implications for drug-drug interaction. Drug Metabolism and Disposition 2000; 28 (8): 930 – 936.

Karetonoidy w Brokułach

Peto- 13

Zeus

Packman

Su003

Marathon

Cavolo

Peto- 6

Eu8- 1

GEM

Brigadar

Majestic

MA- 191

Peto- 7

Baccus

EV6- 1

VI158

Pirate

Green Comet

Shogan

BNC

High Sierra

Atlantic

Genotypes

lutien
beta- carotene

Means, 22 different broccoli genotypes
(mol/100g DW)

10-fold difference

Lutein

Beta-carotene



Działanie przeciwzapalne – ITCs zmniejszają sekrecję cytokin

prozapalnych.



Hamują angiogenezę i tym samych hamują wzrost nowotworów



Zmniejszają toksyczność karcynogenów poprzez hamowanie ich aktywacji.



. Chronią przed uszkodzeniem DNA poprzez wzrost biosyntezy enzymów
ochronnych takich jak GST, reduktaza chinonowa



hamują podziały komórek, których DNA jest uszkodzone



Indukują apoptozę komórek nowotworowych



Maja działanie anty-estrogenowe – Ekspozycja na estrogeny zwiększa
ryzyko raka piersi poprzez wzrost ekspresji genów stymulujących podziały
komórek piersiowych. ITCs hamują ekspresje tych genów.



Jedzenie roślin kapustowatych indukują zmiany hormonalne – zmniejszając
potencjał estrogenów i innych hormonów do indukowania nowotworów.

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Crucifers/
non-smokers

0.70 (ns)

Crucifers/smokers

0.31 (p<0.05)

Crucifers Lower Risk for Lung Cancer

More Effectively in those at high risk

Human Variability

Zhao et al, 2001, Cancer Epi Bio Prev
10:1063-7

Relative risk

Quartile of Crucifer Intake

Fowke et al., Cancer Res. 63: 3980-3986, 2003

Ryzyka raka piersi, rośliny
kapustowate i GSTT1 Null
fenotyp

Human Variability

Chemoprewencyjny działanie
isotiocyjanów i glukozynolanów



Since the early 1960s, both natural and
synthetic isothiocyanates have attracted
considerable and growing attention as
important and effective protectors
against chemical carcinogenesis in a
number of animal models.



Even though only a few glucosinolates
have been examined (largely because
adequate quantities of these compounds
have been unavailable), some appear to
be very effective in inhibiting
carcinogenesis.

PBRC

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History



The history of these developments can
be traced from the comprehensive
review by Hecht and colleagues in
which their work involved the NNK,
which is probably the most prominent
carcinogen derived from cigarettes..



Several isothiocyanates inhibit the
action of this carcinogen (NNK)
through inhibition of its metab olism.

nitrosamine 4-(methylnitrosamino)-1-(3-
pyridyl)-1-butanone

Hecht, SS. Chemoprevention of Cancer by
Isothiocyanates, Modifiers
of Carcinogen Metabolism. J. Nutr. 129: 768S–774S, 1999

Nowotwór pęcherza moczowego



Michaud i wsp. Analizowali 252 chory na nowotwór

pęcherza moczowego, który się rozwiną w okresie

10 lat wśród 47,909 pracowników służby zdrowia.



Nie stwierdzono zależności pomiędzy konsumpcją ,

a ryzkiem



Rak pęcherza:



Całkowite spożycie owoców i warzyw



Tylko owoców



Tylko warzyw



Żółtych lub zielonych warzyw liściastych



Jednakże, ryzyko spadało wraz ze wzrostem

konsumpcji roślin kapustowatych .

Michaud DS, et al. Fruit and vegetable intake and incidence of bladder cancer in a male prospective cohort.
J Natl Cancer Institute 91(7): 605-613, 1999.

Spożycie owoców i warzyw, a ryzyko rak

pęcherza moczowego.

Relative Risk P-value

Fruits and vegetables

0.75

0.25

Fruits

1.12

0.68

Vegetables

0.72

0.09

Yellow vegetables

1.01

0.50

Green leafy vegetables

0.99

0.81

Cruciferous vegetables

0.49

0.008

* The only significant reduction in
relative risk was observed with
cruciferous vegetables.

high intake (5 or more servings/week
versus 1 or less servings/week) of
cruciferous vegetables was
associated with a statistically
significant 51% decrease in bladder
cancer

PBRC



Cohen et al. examined the relationship between
fruit and vegetable consumption and prostate
cancer incidence in men <65 y of age.



High fruit consumption showed no effect on
prostate cancer incidence.



High overall vegetable consumption was
associated with reduced risk.



However, cruciferous vegetables were clearly
protective when risk was adjusted for total
vegetable consumption and other variables.

Nowotwór prostaty

Cohen JH et al. Fruit and vegetable intakes and prostate cancer.
J Natl Cancer Institute 92(1): 61-68, 2000.

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

Also, prostate cancer risk was found to
be reduced by cruciferous vegetable
consumption in a population-based
case-control study carried out in
western Washington state.



Three or more servings per week,
compared to less than one serving of
cruciferous vegetables per week
resulted in a statistically significant
41% decrease in prostate cancer risk.

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Ryzyko raka piersi i białaczki (non-

Hodgkin’s lymphoma)



A case-controlled study in China found that
intake of cruciferous vegetables, measured by
urinary secretion of isothiocyanates, was
inversely related to the risk of breast cancer.



The quartile with the highest intake had only 50%
of the risk of the lowest intake group



In the Nurses’ Health Study, a high intake of
cruciferous vegetables (5 or more servings/week
versus less than two servings/week) was
associated with a 33% lower risk of
non-Hodgkin’s lymphoma.

Any of a large group

of cancers of lymphocytes (white blood cells).

Indukcja QR w wątrobie
szczurów

Matusheski and Jeffery, 2001

*Significantly different from pair fed group (Student’s T-test,

p<0.05).

Mean ± Standard Error

Experiment 1

Experiment 2

Ornish: Diet, PSA



Intensive lifestyle changes may affect the progression of prostate
cancer by Dean Ornish in the September 2005 issue of The Journal of
Urology found, “Intensive lifestyle changes may affect the progression of
early, low grade prostate cancer in men.”  A total of 93 men with elevated
PSA levels (4 to 10 ng/ml), with a Gleason score of less than 7, and who
had not undergone conventional treatments, were split into two groups.
For one year, one group followed a low-fat vegan diet and the other
continued with the American diet (control group).  Because of a rise in PSA
levels or signs of disease progression, 6 in the control group eventually
underwent conventional therapy (surgery, radiation, chemotherapy) – none
in the vegan diet group required further treatment. PSA decreased 4% in
the vegan diet group and rose 6% in the control American-diet group.



Serum (a part of the blood) was taken from the patients and used to grow
prostate cancer cells in the laboratory. The serum from those on the
vegan diet inhibited growth of these cells 8 times more effectively
than did the serum from those on the American diet. The stricter
the patients followed the low-fat vegan diet the better the results with PSA
and cancer cell growth inhibition.

Ornish Quality of Life Study



Urology. 2006 Jan;67(1):125-30. Lifestyle and health-related quality of life of men

with prostate cancer managed with active surveillance.



Daubenmier JJ

, Weidner G, Marlin R, Crutchfield L, Dunn-Emke S, Chi C, Gao B,

Carroll P, Ornish D. Preventive Medicine Research Institute, Sausalito, California 94965,

USA. jennifer.daubenmier@pmri.org

OBJECTIVES: To assess the impact of lifestyle on health-related quality

of life (HR-QOL), perceived stress, and self-reported sexual function in

men with early-stage prostate cancer electing active surveillance.



METHODS: A total of 44 intervention and 49 usual-care control

participants were enrolled in a randomized clinical trial examining the

effects of lifestyle changes on prostate cancer progression. The

intervention consisted of a low-fat, vegan diet, exercise, and stress

management. Participants completed the Medical Outcomes Study

Short Form-36 Health Status Survey (a measure of mental and

physical HR-QOL), the Perceived Stress Scale, the Sexual Function

subscale of the University of California, Los Angeles, Prostate Cancer

Index, and measures of lifestyle behaviors (to yield an overall lifestyle

index) at baseline and 12 months. The data were analyzed using

analysis of variance for repeated measures. The relationship between

lifestyle and QOL was also analyzed using multiple linear regression

analyses.

Ornish Study (continued)



RESULTS: Intervention participants had significantly

improved their lifestyle compared with controls at 12

months. The quality-of-life scores were high across groups

and time points. However, a healthier lifestyle was related

to better QOL at baseline. Participants in both groups

who reported a healthier lifestyle also reported

better mental and physical HR-QOL and sexual

function. Furthermore, participants whose lifestyle

improved over time showed enhanced physical HR-QOL and

decreased perceived stress.



CONCLUSIONS: Men who choose active surveillance for

early-stage prostate cancer are able to make

comprehensive lifestyle changes. Although the average

QOL was already high in this sample, individuals who

improved their lifestyle enhanced their QOL further.

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