LE Magazine July 2003
I3C
Chemoprevention of colon cancer by
Korean food plant components.
Inducible cyclooxygenase (COX-2) and inducible nitric oxide
synthase (iNOS/NOS-2) play pivotal roles as mediators of
inflammation involved in early steps of carcinogenesis in
certain organs. Therefore, chemoprevention is theoretically
possible through inhibition of COX-2 and/or iNOS. In the
present study, we examined the chemopreventive effects of
indole-3-carbinol (I3C), a constituent of cruciferous
vegetables (the family of Cruciferae) such as cabbages,
cauliflowers and broccoli on the multiple intestinal neoplasia
(Min) genetic mouse model, and on mouse colon carcinogenesis
induced by azoxymethane (AOM). The consumption of cruciferous
vegetables such as cabbage, broccoli, and Brussels sprouts has
been shown to have cancer chemopreventive effects in humans
and experimental animals. I3C has been shown to exert a cancer
chemopreventive influence in liver, colon, and mammary tissue
when given before or concurrent with exposure to a carcinogen.
Powdered AIN-76A diets (Harlan Teklad Research Diet, Madison,
USA) containing 100 or 300 ppm I3C (group 1 or 2) or the same
pellet diets without supplement (group 3) were fed to
six-week-old male C57BL/6J-Apc(Min)(/+) (Min/+) mice (The
Jackson Laboratory, Bar Harbor, ME, USA) for 10 weeks. In
addition the same diets were given to wild-type normal
C57BL/6J-Apc(Min)(/+) littermates after AOM initiation (groups
4-7: 10 mice in each group) for 32 weeks from week four. At 16
weeks of age, all Min/+ mice (groups 1-3) were sacrificed for
assessment of intestinal polyp development. The incidences of
the colonic adenomatous polyps in the groups 1-3 were 60%
(12/20), 60% (15/25) and 84% (21/25), respectively. A
decreasing tendency in multiplicities of the colonic
adenomatous polyps in group 1 (I3C 100 ppm; 0.85 +/- 0.22;
61%) and group 2 (I3C 300 ppm; 1.32 +/- 0.28; 94%) was
observed when compared with group 3 (control; 1.40 +/- 0.21;
100%). Total number of aberrant crypt foci (ACF)/colon or
aberrant crypts (AC)/colon in wild-type mice of group 4 or 5
were decreased significantly compared with those of the AOM
alone group (group 6) (P < 0.01). These results suggest
that I3C may be a potential chemopreventive agent for colon
cancer.
Mutat Res 2003
Feb-Mar;523-524:99-107
Modulation of vinca-alkaloid induced
P-glycoprotein expression by indole-3-carbinol.
The over-expression of mdr-1 gene transcript P-glycoprotein
(P-gp), responsible for multiple drug resistance, is one of
the major obstacles in cancer chemotherapy. In the present
study, indole-3-carbinol (I3C), a well-known chemopreventive
agent present in cruciferous vegetables, has been evaluated
for its potential to modulate the over-expression of P-gp
induced by vinblastine or vincristine, which are known
inducers of mdr-1 gene. The results revealed that I3C
significantly reversed the over-expression of P-gp in
vinca-alkaloid induced drug resistance as evident by Western
blotting using monoclonal antibody (clone JSB1). Quantization
of immunostained tissue sections using image analysis
technique revealed that vinblastine/vincristine induced
overexpression of P-gp was effectively reversed by I3C. The
present investigation suggests that I3C can significantly
inhibit the P-gp over-expression and may have utility as a
dietary adjuvant in the treatment of cancer for the reversal
of multiple drug resistance.
Cancer Lett 2003 Jan
28;189(2):167-73
Serum total homocysteine increases
with the rapid proliferation rate of tumor cells and decline
upon cell death: a potential new tumor marker.
BACKGROUND: We were interested to know why cancer patients
are frequently associated with elevated circulating total
homocysteine (tHcy) even though they are not treated with
anti-folate drugs. METHODS: We employed tissue cultures to
compare both the homocysteine (Hcy)-released and production of
tumor markers between tumor and normal cell lines. RESULTS: We
detected much higher concentrations of homocysteine (Hcy)
released by the tumor cells. However, much less difference was
found between normal and tumor cell lines when Hcy
concentration was expressed per the same number of cells.
During the cell culture, the increase of Hcy and the increase
of tumor marker concentration paralleled each other for the
first seven days. After the seventh day of the culture when
cells started dying, tumor markers continued to rise, whereas
levels of Hcy and cell numbers leveled off. We found that the
serum concentration of Hcy fluctuated in circulation
coinciding with that of tumor marker in individual cancer
patients unless taking anti-neoplastic drug. CONCLUSIONS: The
elevation of tHcy concentration may be caused by the rapid
tumor cell proliferation and reflect only the number of live
cells. Serum Hcy may be a potentially useful tumor marker to
monitor tumor activity.
Clin Chim Acta 2002
Jul;321(1-2):55-62
Effect of some indole derivatives on
xenobiotic metabolism and xenobiotic-induced toxicity in
cultured rat liver slices.
In this study the effect of some indole derivatives on
xenobiotic metabolizing enzymes and xenobiotic-induced
toxicity has been examined in cultured precision-cut liver
slices from male Sprague-Dawley rats. While treatment of rat
liver slices for 72 hours with 2-200 microM of either
indole-3-carbinol (I3C) or indole-3-acetonitrile (3-ICN) had
little effect on cytochrome P-450 (CYP)-dependent enzyme
activities, enzyme induction was observed after in vivo
administration of I3C. The treatment of rat liver slices with
50 microM 3,3'-diindolylmethane (DIM; a dimer derived from I3C
under acidic conditions) for 72 hours resulted in a marked
induction of CYP-dependent enzyme activities. DIM appears to
be a mixed inducer of CYP in rat liver slices having effects
on CYP1A, CYP2B and CYP3A subfamily isoforms. Small increases
in liver slice reduced glutathione levels and glutathione
S-transferase activity were also observed after DIM treatment.
While aflatoxin B1 and monocrotaline produced a
concentration-dependent inhibition of protein synthesis in
72-hour-cultured rat liver slices, cytotoxicity was markedly
reduced in liver slices cultured with 50 microM DIM. These
results demonstrate that cultured rat liver slices may be
employed to evaluate the effects of chemicals derived from
cruciferous and other vegetables on CYP isoforms. In addition,
liver slices can also be utilized to examine the ability of
such chemicals to modulate xenobiotic-induced toxicity.
Food Chem Toxicol 1999
Jun;37(6):609-18
Prevention of chromosomal aberration
in mouse bone marrow by indole-3-carbinol.
In this study, we report the protective effect of
indole-3-carbinol (I3C), one of the glucobrassicin derivative
isolated from cruciferous vegetables against cyclophosphamide-
induced chromosomal aberrations in mouse bone marrow cells.
The three test doses namely 1000, 500 and 250 mg/kg b.wt. of
I3C provided protection when given 48 h prior to the single
i.p. administration of cyclophosphamide (50 mg/kg). I3C alone
did not induce chromosomal aberrations at the test doses of
1000 and 500 mg/kg b.wt. Thus, tested glucobrassicin
derivative seems to have a preventive potential against
cyclophosphamide induced chromosomal aberrations in Swiss
mouse bone marrow cells at the doses tested.
Toxicol Lett 1999 Jun
1;106(2-3):137-41
Serum folate, homocysteine and
colorectal cancer risk in women: a nested case-control
study.
Accumulating evidence suggests that folate, which is
plentiful in vegetables and fruits, may be protective against
colorectal cancer. The authors have studied the relationship
of baseline levels of serum folate and homocysteine to the
subsequent risk of colorectal cancer in a nested case-control
study including 105 cases and 523 matched controls from the
New York University Women's Health Study cohort. In univariate
analyses, the cases had lower serum folate and higher serum
homocysteine levels than controls. The difference was more
significant for folate (P < 0.001) than for homocysteine (P
= 0.04). After adjusting for potential confounders, the risk
of colorectal cancer in the subjects in the highest quartile
of serum folate was half that of those in the lowest quartile
(odds ratio, OR = 0.52, 95% confidence interval, CI =
0.27-0.97, P-value for trend = 0.04). The OR for the highest
quartile of homocysteine, relative to the lowest quartile, was
1.72 (95% CI = 0.83-3.65, P-value for trend = 0.09). In
addition, the risk of colorectal cancer was almost twice as
high in subjects with below-median serum folate and
above-median total alcohol intake compared with those with
above-median serum folate and below-median alcohol consumption
(OR = 1.99, 95% CI = 0.92-4.29). The potentially protective
effects of folate need to be confirmed in clinical trials.
Br J Cancer 1999
Apr;79(11-12):1917-22
The effect of indole-3-carbinol and
sulforaphane on a prostate cancer cell line.
BACKGROUND: Cruciferous vegetable consumption is inversely
related to the incidence of prostate cancer. We examined the
effect of indole-3-carbinol (I3C) and of sulforaphane
(constituents of cruciferous vegetables) on cell proliferation
of a PC-3 prostate cancer cell line, in order to observe if an
inhibitory effect might be detected in vitro. METHODS: PC-3
prostate cancer cells were cultured in 96-well microtitre
plates. Indole-3-carbinol concentrations ranging from 0.1
mmol/L to 0.8 mmol/L or sulforaphane concentrations ranging
from 0.01 mmol/L to 0.06 mmol/L were added to the wells. Cell
proliferation was measured by colorimetric assay and results
were based on the mean value of triplicate experiments. Data
are presented as medians and interquartile ranges and were
analysed using the Mann-Whitney U-test. RESULTS: Cell
proliferation in PC-3 prostate cancer cells was significantly
inhibited by I3C and sulforaphane at media concentrations of
0.2 mmol/L and 0.02 mmol/L, respectively. CONCLUSION: Both
compounds inhibited the proliferation of prostate cancer cells
in a dose-dependant manner. These findings may help explain
the observed protective effect of cruciferous vegetables in
relation to prostate cancer.
ANZ J Surg 2003 Mar;73(3):154-6
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