Allyl isothiocyanate (AITC) is organosulfur compounds found abundantly
in cruciferous vegetables and responsible for the pungent taste of
mustard, horseradish, wasabi, etc
1. Allyl isothiocyanate (AITC) and prostate cancer
In the study to demonstrate that allyl isothiocyanate
(AITC), a constituent of cruciferous vegetables, significantly inhibits
proliferation of cultured PC-3 (androgen-independent) and LNCaP
(androgen-dependent) human prostate cancer cells in a dose-dependent manner with an IC(50) of approximately 15-17 micro, found that a 24 h exposure of PC-3 and LNCaP cells to an apoptosis-inducing
concentration of AITC (20 micro M) resulted in a significant decrease
(31-68%) in the levels of anti-apoptotic protein Bcl-2 in both cell
lines, and approximately 58% reduction in Bcl-X(L) protein expression in
LNCaP cells. In conclusion, it seems reasonable to hypothesize that
AITC, and possibly other ITCs, may find use in the treatment of human
prostate cancers(1).
2. Allyl isothiocyanate (AITC) and Breast cancer
Allyl isothiocyanate (AITC),
a member of the isothiocyanate (ITC) family found in a constituent of
cruciferous vegetables, possesses anticancer activity and induces
apoptosis in various types of human cancer cell lines. According the
China Medical University in the study on exploring the mechanisms
underlying AITC-induced apoptosis in MDA-MB-468 human breast cancer cells in vitro, showed that
AITC-promoted G2/M phase and AITC-triggered apoptosis correlate with the activation of phosphorylation of ERK in MDA-MB-468 cells. AITC is a potential agent for applcation in the treatment of human breast cancer(2).
3. Antimicrobial Activities of Isothiocyanates
Food-borne human infection with Campylobacter jejuni is a medical
concern in both industrialized and developing countries. In the study to
investigste the bacteriostatic and bactericidal activities of two
phytochemicals, allyl-isothiocyanate (AITC),
and benzyl isothiocyanate (BITC), against 24 C. jejuni isolates from
chicken feces, human infections, and contaminated foods, as well as two
reference strains NCTC11168 and 81-176. AITC
and BITC displayed a potent antibacterial activity against C. jejuni,
found that both compounds are bactericidal rather than bacteriostatic,
and highlighted the role of GGT enzyme in the survival rate of C. jejuni
exposed to ITC(3).
4. DNA damage and repair in adults consuming allyl isothiocyanate
Allyl isothiocyanate (AITC) is a dietary component with possible anticancer effects, though much information about AITC and cancer has been obtained from cell studies. In the study to assess the effect of AITC on DNA integrity in vivo, a crossover study was conducted. Adults (n=46) consumed AITC, AITC-rich
vegetables [mustard and cabbage (M/C)] or a control treatment with a
controlled diet for 10 days each, Indicated that DNA damage appeared to
be induced in the short term by AITC and AITC-rich products, but that damage disappeared quickly, and neither AITC nor AITC-rich products affected DNA base excision repair(4).
5. Allyl isothiocyanate as a cancer chemopreventive phytochemical
Allyl isothiocyanate (AITC),
which occurs in many common cruciferous vegetables, is widely and often
frequently consumed by humans. According to the study by the Roswell
Park Cancer Institute,
AITC may be most effective in the bladder as a cancer chemopreventive compound. AITC
at high-dose levels also exhibit a low degree of cytotoxicity and
genotoxicity in animal studies, but such adverse effects are unlikely in
humans exposed to dietary levels of AITC. Overall, AITC
exhibits many desirable attributes of a cancer chemopreventive agent,
and further studies are warranted in order to elucidate its mechanism of
action and to assess its protective activity in humans(5).
6. Allyl isothiocyanate and bladder cancer
Bladder cancer is one of the common human
cancers and also has a very high recurrence rate. According to the study
by the Roswell Park Cancer Institute, a low oral dose of AITC
(1 mg/kg) significantly inhibited the development and muscle invasion
of the orthotopic bladder cancers but was ineffective against the
subcutaneous xenografts of the same cancer cells in the same animals.
This differential effect was explained by our finding that urinary
levels of AITC equivalent were two to
three orders of magnitude higher than that in the plasma and that its
levels in the orthotopic cancer tissues were also three orders of
magnitude higher than that in the subcutaneous cancer tissues. Moreover,
we show that AITC is a multi-targeted agent against bladder cancer(6).
7. Isothiocyanates and oxidative stress
The choroid plexuses (CPs) form the
blood-cerebrospinal fluid (CSF) barrier (BCSFB) and play an important
role in maintaining brain normal function and the brain response to
injury. According to the study by the University of Michigan,
Sulforaphane (SF) significantly reduced H(2)O(2)-induced BCSFB
disruption as assessed by transepithelial electrical resistance (29 ± 7%
reduction vs. 92 ± 2% decrease in controls) and [(3)H]mannitol
permeability. Allyl-isothiocyanate (AITC)
had a similar protective effect. H(2)O(2)-induced epithelial cell death
was also reduced by these isothiocyanates. In primary CP cells, SF and AITC
reduced cell death by 42 ± 3% and 53 ± 10%, respectively. Similar
protection was found in a CP cell line Z310. Protection was only found
with pretreatment for 12-48 h and not with acute exposure (1 h). The
protective effects of SF and AITC were
associated with Nrf2 nuclear translocation and upregulated expression of
antioxidative systems regulated by Nrf2, including heme oxygenase-1,
NAD(P)H quinine oxidoreductase, and cysteine/glutamate exchange
transporter(7).
8. Anti-inflammatory potential of allyl-isothiocyanate
In the study to investigate the underlying mechanisms of the potential anti-inflammatory properties of allyl-isothiocyanate (AITC) in vitro and in vivo, found that AITC
was slightly less potent than sulforaphane (used as a positive control)
in down-regulating inflammation in LPS-stimulated macrophages. A
significant increase in nuclear Nrf2 and heme-oxygenase 1 gene
expression and only a moderate down-regulation of interleukin-1β and
microRNA-155 levels due to AITC was found in mouse liver. Present data suggest that AITC
exhibits potent anti-inflammatory activity in cultured macrophages in
vitro but has only little anti-inflammatory activity in mice in vivo(8).
9. Allyl isothiocyanate (AITC) - the inducer of PON1
In the study to test the
ability of structure-related isothiocyanates to induce the
antiatherogenic enzyme paraoxonase-1 (PON1) in cultured hepatocytes,
conducted by the Christian-Albrechts-University of Kiel, Kiel, indicated
that Allyl isothiocyanate (AITC),
phenylethyl isothiocyanate (PEITC), and sulforaphane (SFN), but not
butyl isothiocyanate (BITC) resulted in dose-dependent induction of PON1
transactivation in Huh7 cells in vitro. Induction of PON1 due to AITC was inhibited by the selective peroxisome proliferator-activated receptor γ-antagonist T0070907. AITC
was used in a subsequent in vivo study in mice (n = 10 per group,
Western-type diet) to test its PON1 inducing activity. Unlike in
cultured hepatocytes, AITC
supplementation (15 mg/kg body weight) did not increase hepatic PON1
mRNA and protein levels in mice. Thus, it is suggested that AITC may be a potent inducer of PON1 in vitro, but not in mouse liver in vivo(9).
10. Allyl isothiocyanate (AITC) and the antioxidant enzymes in cultured fibroblasts
The isothiocyanate
sulforaphane (SFN) has been shown to induce phase 2 and antioxidant
enzymes in cultured cells and in vivo via a Nrf2 dependent signal
transduction pathway. According to the study by the
Christian-Albrechts-University Kiel, not only SFN but also other
aliphatic and aromatic isothiocyanates such as AITC, BITC and PEITC induce phase 2 and antioxidant enzymes in cultured fibroblasts(10).
**11. Allyl isothiocyanate (AITC) toxicity
In the study to assess the Subchronic toxicity of a horseradish extract (HRE), consisting mainly of a mixture of allyl isothiocyanate (AITC)
and other isothiocyanates, with administration at concentrations of 0,
0.0125, 0.025 and 0.05% of HRE in drinking water for 13 weeks to male
and female F344 rats, found that on histopathological assessment,
papillary/nodular hyperplasia of bladder mucosa was observed in 0.05%
HRE and AITC males and females, in
addition to simple mucosal hyperplasia found in all treated groups.
Based on the above findings, no-observed-adverse-effect levels (NOAELs)
were estimated to be below 0.0125% of HRE for both males and females,
corresponding to 9.4 and 8.0 mg/kg body weight/day, respectively, and
there appeared to be comparable toxicological properties of HRE to AITC, such as the inductive effect of significant proliferative lesions in the urinary bladder(11).
12. Allyl isothiocyanate and gastrointestinal contractility
In the study to investigate the effect of AITC on intestinal motility, conducted by the University of Naples Federico II, indicated that AITC,
depending, in vitro, on the regions of gut examined and, in vivo, on
the route of administration, exerted both stimulatory and inhibitory
effects on intestinal motility, which were not sensitive to TRPA1
channel antagonists. The proposition that TRPA1 channels are the primary
targets for AITC to induce contraction should be revised.(12).
13. Allyl isothiocyanate (AITC) and cancers
Allyl isothiocyanate (AITC)occurs
in many commonly consumed cruciferous vegetables and exhibits
significant anti-cancer activities. According to the study by the
California Institute of Technology, AITC
induced mitochondrion-mediated apoptosis, as shown by cytochrome c
release from mitochondria to cytoplasm, activation of caspase-9 and
caspase-3, and formation of TUNEL-positive cells. Inhibition of
caspase-9 blocked AITC-induced apoptosis. Moreover, we found that apoptosis induction by AITC
depended entirely on mitotic arrest and was mediated via Bcl-2
phosphorylation at Ser-70. Pre-arresting cells in G(1) phase by
hydroxyurea abrogated both AITC-induced mitotic arrest and Bcl-2 phosphorylation. Overexpression of a Bcl-2 mutant prevented AITC from inducing apoptosis. We further showed that AITC-induced Bcl-2 phosphorylation was caused by c-Jun N-terminal kinase (JNK), and AITC activates JNK(13).
14. Allyl isothiocyanate and human colorectal cancer
Allyl isothiocyanate (AITC) is a constituent of cruciferous vegetables that exhibits antitumor activity. In this study, AITC
was shown to inhibit the proliferation of human metastatic colorectal
adenocarcinoma SW620 cells in vitro by inducing cell cycle arrest at the
G2/M phase. According to the study by The Chinese University of Hong
Kong, Shatin, upon prolonged exposure, AITC
induced caspase-mediated apoptosis in SW620 cells. The apoptotic
process was evidenced by the activation of initiator caspases (-8 and
-9) and effector caspases (-3 and -7), and the cleavage of
poly(ADP-ribose) polymerase (PARP). The antitumor activity of AITC was further demonstrated in a SW620 xenograft in vivo. Taken together, the results suggest that AITC is a potential candidate for future research in chemoprevention and chemotherapy(14).
15. Allyl isothiocyanate and human brain malignant glioma
Isothiocyanates (ITCs) are present as glucosinolates in various cruciferous vegetables. Allyl isothiocyanate (AITC) is one of the common naturally occurring isothiocyanates. According to the study by the National Chung Hsing University, AITC markedly reduced the CDK1/cyclin B activity and protein levels by CDK1 activity assay and Western blot analysis. AITC-induced
apoptotic cell death and this evidence was confirmed by morphological
assessment and DAPI staining. Pretreatment with specific inhibitors of
caspase-3 (Z-DEVE-FMK) and -9 (Z-LEHD-FMK) significantly reduced
caspase-3 and -9 activity in GBM 8401 cells. Western blot analysis and
colorimetric assays also displayed that AITC
caused a time-dependent increase in cytosolic cytochrome c,
pro-caspase-9, Apaf-1, AIF, Endo G and the stimulated caspase-9 and -3
activity. Our results suggest that AITC
is a potent anti-human brain malignant glioma drug and it shows a
remarkable action on cell cycle arrest before commitment for apoptosis
is reached(15).
16. Allyl isothiocyanate and stress-responses
The main pungent component of wasabi (Eutrema japonica) is known to be isothiocyanate and its derivatives, volatile substances. Allyl isothiocyanate (AITC) accounts for more than half of isothiocyanate derivatives. According to the study posted in J Toxicol Sci. 2010 Aug;35(4):583-9, showed that administration of AITC increased the number of neutrophil on days 8-10 by 61-112%. AITC
did not change the number of eosinophil and basophil. Plasma
corticosterone concentrations during the experimental period were
4.7-8.4 times significantly higher in the AITC group than in the control group, indicating that AITC induced stress-responses(16).
17. Allyl isothiocyanate (AITC) hepaprotective effects
In the study to investigate possible protective effect of allyl isothiocyanate (AITC)
in nitrite- and nitrosamine-treated human hepatoma cells (HepG2) with
the evaluation by cytotoxic effects and genotoxic effects determined by
the single-cell gel electrophoresis (SCGE), found that Allyl isothiocyanate
treatment enhanced cell viability and reduced intracellular reactive
oxygen species (ROS) production in both nitrite- and nitrosamine-treated
cells significantly. In SCGE, when compared to untreated control cells,
all of the treated groups caused increases in the tail intensity (%)
such as nitrite at 17%, N-nitrosodimethylamine (NDMA) at 279%,
N-nitrosodiethylamine (NDEA) at 324%, and N-nitrosomorpholine (NMOR) at
288%. Allyl isothiocyanate reduced the
tail intensity caused by nitrite 36%, by NDMA 36%, by NDEA 49%, and by
NMOR 32%, respectively, when compared to each individual toxic
compound-treated group. In conclusion, AITC protected HepG2 cells against cytotoxic and genotoxic effects caused by nitrite and the nitrosamines(17).
18. Allyl isothiocyanate and pests
In the study to investigate the effects of extraction of allyl isothiocyanate
from horseradish (Armoracia rusticana) and its fumigant insecticidal
activity on four stored-product pests of paddy, found that good
insecticidal efficacy of AITC against the four stored-product pests, with non-gaseous residuals on stored products. AITC obtained from A. rusticana may be an alternative to phosphine and methyl bromide against the four pest species(18).
19. Antiangiogenic and proapoptotic activities of allyl isothiocyanate
In the studyt to investigate the antiangiogenic and proapoptotic effects of mustard essential oil containing allyl isothiocyanate (AITC)
and explore its mechanism of action on Ehrlich ascites tumor (EAT)
cells with Swiss albino mice transplanted with EAT cells, found that
AITC significantly reduced ascites secretion and tumor cell
proliferation by about 80% and inhibited vascular endothelial growth
factor expression in tumor-bearing mice in vivo. It also reduced vessel
sprouting and exhibited potent antiangiogenic activity in the
chorioallantoic membrane and cornea of the rat. AITC arrested the growth of EAT cells by inducing apoptosis and effectively arrested cell cycle progression at the G1 phase(19).
20. Allyl isothiocyanate and liver cancer
Glucosinolates. Sinigrin, the predominant aliphatic glucosinolate in cruciferous vegetables, is hydrolyzed to yield allyl isothiocyanate (AITC) to determine the inhibitory effects of AITC
and its NAC conjugate on cell proliferation, the expression of matrix
metalloproteinases (MMPs), adhesion, invasion, and migration in SK-Hep 1
human hepatoma cells, indicated that AITC and NAC-AITC suppress SK-Hep 1 cell proliferation in a dose-dependent manner; by 25% and 30% for 10 microM AITC and 10 microM NAC-AITC, respectively(20).
21. Isothiocyanates and the immune system
Administration of allyl isothiocyanate (AITC)
and phenyl isothiocyanate (PITC) was found to stimulate the
immunological response in Balb/c mice. According to the study by the
Amala Cancer Research Centre, indicated that treatment with AITC
and PITC along with the antigen sheep red blood cells (SRBC) produced
an enhancement in the circulating antibody titer and the number of
plaque forming cells (PFC) in the spleen. Maximum number of PFC
(1329PFC/10(6) spleen cells) for AITC and
PITC (1218PFC/10(6) spleen cells) was obtained on the 5th day. These
results indicate the immunomodulatory activities of the two naturally
occurring isothiocyanates namely, AITC and PITC(21).
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Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/12771033
(2) http://www.ncbi.nlm.nih.gov/pubmed/23008020
(3) http://www.ncbi.nlm.nih.gov/pubmed/22919644
(4) http://www.ncbi.nlm.nih.gov/pubmed/22902324
(5) http://www.ncbi.nlm.nih.gov/pubmed/19960458
(6) http://www.ncbi.nlm.nih.gov/pubmed/19955395
(7) http://www.ncbi.nlm.nih.gov/pubmed/22573102
(8) http://www.ncbi.nlm.nih.gov/pubmed/21692985
(9) http://www.ncbi.nlm.nih.gov/pubmed/22131196
(10) http://www.ncbi.nlm.nih.gov/pubmed/21109004
(11) http://www.ncbi.nlm.nih.gov/pubmed/22129740
(12) http://www.ncbi.nlm.nih.gov/pubmed/21955242
(13) http://www.ncbi.nlm.nih.gov/pubmed/21778226
(14) http://www.ncbi.nlm.nih.gov/pubmed/21472349
(15) http://www.ncbi.nlm.nih.gov/pubmed/20596632
(16) http://www.ncbi.nlm.nih.gov/pubmed/20686346
(17) http://www.ncbi.nlm.nih.gov/pubmed/20448263
(18) http://www.ncbi.nlm.nih.gov/pubmed/19459178
(19) http://www.ncbi.nlm.nih.gov/pubmed/19223371
(20) http://www.ncbi.nlm.nih.gov/pubmed/16565438
(21) http://www.ncbi.nlm.nih.gov/pubmed/19180807
Please note that all articles written by Kyle. J. Norton are for information and education only, please consult with your doctor or related field specialist before applying. http://diseases-researches.blogspot.ca/
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