Protective effect of dietary tomatine against dibenzo[a,l]pyrene (DBP)-induced liver and stomach tumors in rainbow trout

Western Regional Research Center, Agricultural Research Service, U.S. Department of Agriculture, Albany, CA 94710, USA.
Molecular Nutrition & Food Research (Impact Factor: 4.6). 12/2007; 51(12):1485-91. DOI: 10.1002/mnfr.200700176
Source: PubMed
ABSTRACT
The potential anti-carcinogenic effects of tomatine, a mixture of commercial tomato glycoalkaloids alpha-tomatine and dehydrotomatine (10:1), were examined in the rainbow trout chemoprevention model. Prior to the chemoprevention study, a preliminary toxicity study revealed that tomatine in the diet fed daily at doses from 100 to 2000 parts per million (ppm) for 4 weeks was not toxic to trout. For the tumor study, replicate groups of 105 trout were fed diets containing dibenzo[a,l]pyrene (DBP) alone (224 ppm), (N = 3), DBP plus tomatine at 2000 ppm (N = 2), tomatine alone (N = 2), or control diet (N = 2) for 4 weeks. The fish were then returned to control diet for 8 months and necropsied for histopathology. Dietary tomatine was found to reduce DBP-initiated liver tumor incidence from 37.0 to 19.0% and stomach tumor incidence from 46.4 to 29.4%. Tomatine also reduced stomach tumor multiplicity. The tomatine-containing diets did not induce mortality, change in fish weights, or liver weights. No adverse pathological effects in the tissues of the fish on the tomatine diets were observed. Dose-response and chemopreventive mechanisms for tomatine protection remain to be examined. This is the first report on the anticarcinogenic effects of tomatine in vivo.

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Available from: Tammie Mcquistan
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Mol. Nutr. Food Res. 2007, 51, 1485 1491 DOI 10.1002/mnfr.200700176
Research Article
Protective effect of dietary tomatine
against dibenzo[a,l]pyrene (DBP)-induced liver
and stomach tumors in rainbow trout
Mendel Friedman
1
, Tammie McQuistan
2
, Jerry D. Hendricks
3
, Cliff Pereira
4
and George S. Bailey
2
1
Western Regional Research Center, Agricultural Research Service, USDA, Albany, CA, USA
2
Linus Pauling Institute and Department of Environmental Toxicology, Oregon State University, Corvallis,
OR, USA
3
Marine Freshwater and Biomedical Sciences Center and Department of Environmental Toxicology,
Oregon State University, Corvallis, OR, USA
4
Department of Statistics and Environmental Health Sciences Center, Oregon State University, Corvallis,
OR, USA
The potential anti-carcinogenic effects of tomatine, a mixture of commercial tomato glycoalkaloids
a-tomatine and dehydrotomatine (10:1), were examined in the rainbow trout chemoprevention model.
Prior to the chemoprevention study, a preliminar y toxicity study revealed that tomatine in the diet fed
daily at doses from 100 to 2000 parts per million (ppm) for 4 weeks was not toxic to trout. For the
tumor study, replicate groups of 105 trout were fed diets containing dibenzo[a,l]pyrene (DBP) alone
(224 ppm), (N = 3), DBP plus tomatine at 2000 ppm (N = 2), tomatine alone (N = 2), or control diet
(N = 2) for 4 weeks. The fish were then returned to control diet for 8 months and necropsied for histo-
pathology. Dietary tomatine was found to reduce DBP-initiated liver tumor incidence from 37.0 to
19.0% and stomach tumor incidence from 46.4 to 29.4%. Tomatine also reduced stomach tumor mul-
tiplicity. The tomatine-containing diets did not induce mortality, change in fish weights, or liver
weights. No adverse pathological effects in the tissues of the fish on the tomatine diets were observed.
Dose-response and chemopreventive mechanisms for tomatine protection remain to be examined.
This is the first report on the anticarcinogenic effects of tomatine in vivo.
Keywords: Dibenzopyrene / Rainbow trout / Tomatine / Tomatoes / Tumor prevention /
Received: May 16, 2007; revised: July 12, 2007; accepted: July 14, 2007
1 Introduction
Tomato plants (Lycopersicon esculentum) synthesize the
glycoalkaloids dehydrotomatine and a-tomatine, possibly
as a defense against bacteria, fungi and viruses, and insects.
[13], as reviewed in [4]. Commercial tomatine used in this
study is a l10:1 mixture of a-tomatine and dehydrotoma-
tine (Fig. 1) [57]. The structure of dehydrotomatine is
similar to that of a-tomatine, in that the former molecule
has a double bond in the steroidal ring B of the aglycone.
Note that both tomato glycoalkaloids have the same tetra-
saccharide side chain. The tomato glycoalkaloid a-tomatine
has a tetrasaccharide side chain attached to the aglycone
tomatidine, whereas the second glycoalkaloid present in
tomato plants called dehydrotomatine has the same tetra-
saccharide side chain attached to the aglycone tomatidenol.
Beneficial effects of tomatine include lowering choles-
terol and triglycerides, enhancing the immune system, and
antibiotic activities. We previously reported that dietary
tomatine decreased plasma LDL cholesterol in hamsters
fed a high saturated fat, high-cholesterol diet by 41% and
plasma triglyceride concentrations by 47% [8]. Similar ben-
eficial effects were observed with high-tomatine green
tomato diets [9]. Because tomatine alone reduced both diet-
ary cholesterol bioavailability and endogenous cholesterol,
the data suggests that tomatine forms an insoluble complex
with cholesterol from both dietary cholesterol and from
endogenous cholesterol produced by the liver, which enters
the digestive tract via the enterohepatic circulation.
Correspondence: Dr. Mendel Friedman, Western Regional Research
Center, Agricultural Research Service, USDA, Albany, CA 94710,
USA
E-mail: mfried@pw.usda.gov
Fax: +1-510-559-5777
Abbreviations: DBP, dibenzo[a,l]pyrene; OTD, Oregon Test Diet;
ppm, parts per million
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M. Friedman et al. Mol. Nutr. Food Res. 2007, 51, 1485 1491
The reported immunopotentiating effect of tomatine of
T-cell mediated regression of lymphoid experimental
tumors (EG7-Ova) may be the result of costimulation of
CD80 and CD86 to induce antigen-specific cellular
immunity [10]. Because tomatine induced antigen-specific
cellular immunity in mice, the authors suggest that tomatine
possesses remarkable potential as a vaccine adjuvant for
infectious diseases as well as for cancer immunotherapy.
Recently, Ito et al. [1] found that the antibiotic effect of
tomatine against the fungal pathogen Fusarium oxysporum
involves activation of phosphotyrosine kinase and G-pro-
tein signaling pathways leading to Ca
2+
elevation and accu-
mulation of reactive-oxygen species (ROS). In related stud-
ies, Simons et al. [2] found that the mode of action of a-
tomatine towards yeast cells involving cell membrane per-
meilization is distinct from that of the aglycone tomatidine
that lacks the tetrasaccharide side chain.
Using a microculture tetrazolium (MTT) in vitro assay,
we previously reported that tomatine is a strong inhibitor of
growth for both human colon and liver cancer cell lines, as
evidenced by the concentration-dependent (0.1 to 100 lg/
mL) inhibition of HT29 colon cancer cells at levels ranging
from 38.0 to 81.5%, and of human HepG2 cancer cells,
from 46.3 to 89.2% [11]. The antiproliferative activity
against human liver cancer cells at a tomatine concentration
of 1 lg/mL was higher than the corresponding activity
observed with the commercial anticancer drug doxorubicin.
To further define the potential value of tomatine in the in
vivo chemoprevention of cancer, the objective of the present
study was to determine the ability of dietary tomatine to
inhibit dibenzo[a,l]pyrene (DBP)-induced liver and stom-
ach tumors in the trout model determined in a long-term
feeding study. As a prerequisite to the tumor study, the acute
toxicity of tomatine added to a control diet fed orally to
rainbow trout was determined. DBP, a planar polyaromatic
hydrocarbon, is a potent environmental hydrocarbon [12]
and has been identified as a combustion product in coal
smoke [13] and tobacco smoke [14]. DBP is a potent tumor
initiator in mouse skin and rat mammary gland [12, 15, 16].
In the rainbow trout model, DBP initiates tumors in multi-
organs; liver, stomach and swimbladder [1719].
The rainbow trout model is highly sensitive to diverse
chemical carcinogens and is a statistically powerful verte-
brate model used in many comparative studies of chemical
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Figure 1. Stereochemistry of the tetrasaccharide side chain of tomatine attached to the aglycone tomatidine, of the identical tetra-
saccharide side chain of dehydrotomatine attached to the aglycone tomatidenol, and of cholesterol. Anticarcinogenic activities of
tomatine may result from formation of 1:1 complexes with cholesterol [4], disruption of cancer cell membranes [11, 39], and stimula-
tion of the immune system [10].
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Mol. Nutr. Food Res. 2007, 51, 1485 1491
carcinogenesis and its modulation by dietar y inhibitors
[1727].
2 Materials and methods
2.1 Test compounds
Tomatine was purchased from Sigma Chemical Company
(St. Louis, MO, USA). Dibenzo[a,l]pyrene was obtained
from the National Cancer Institute (NCI) Reference Stand-
ard Repository in Kansas City, MO,USA. Handling and stor-
age of this potent multi-organ carcinogen was in accordance
with National Institutes of Health and Oregon State Univer-
sity guidelines for Moderate Hazard Carcinogens. Both
tomatine and DBP were dissolved in the oil component of
the trout semi-synthetic Oregon Test Diet (OTD), [23, 25].
The concentrations of tomatine and DBP are expressed in
parts per million (ppm) relative to the dry weight portion of
the diet. DBP is light sensitive and was handled in subdued
lighting. Diets with test compounds were prepared every
2 weeks and stored at 208C until a day prior to feeding
when the diets were moved to 48C. DBP is stable in diets
stored at 208C for up to 2 years [28].
2.2 Animals
Shasta strain rainbow trout were spawned, reared and
treated at the Sinnhuber Aquatic Research Laboratory
(SARL), Oregon State University as described [23, 26]
under protocols from the National Institute of Health (NIH)
and received approval from our Institutional Animal Care
and Use Committee. Fry were fed the OTD from onset of
feeding to dietary initiation [25].
2.3 Tomatine acute toxicity study
Because 2000 ppm tomatine in the diet was a dose tolerated
by hamsters, we carried out a range-finding experiment up
to this level in the trout diet to guide selection of future
doses for a dose-response tumor chemoprevention study in
trout. Tomatine over a range of doses (100, 500, 1000, and
2000 ppm) was added to the oil component of the diet and
fed daily for 4 weeks to groups of 50 trout each. One tank of
50 trout was fed OTD alone as a control group. During the
exposure, mortalities were recorded on a daily basis. At the
end of the 4 weeks, 10 trout per tank were removed and
overdosed with tricaine methanesulfonate, MS-222 [17].
The livers were removed, weighed, and examined for abnor-
mality.
2.4 Cancer chemoprevention study
A total of 945 trout were allocated to 9 tanks, N = 105 each
tank. Trout acclimatized to the tanks for one week prior to
start of the carcinogen exposure. Duplicate tanks received
the control diet (OTD), tomatine (2000 ppm), tomatine
(2000 ppm) and DBP (224 ppm), and triplicate tanks
received only DBP (224 ppm). After 4 weeks of dietary
exposure, all groups were returned to OTD for 8 months
and necropsied for gross pathology and histopathological
examination.
2.5 Tumor histology
Trout were sacrificed by MS-222 overdose and liver and
stomach tumor development were quantified as described
[24, 25]. Tissues were examined under a dissecting scope
for gross tumors (F0.5 mm diameter), fixed in Bouin's sol-
ution and processed by routine histological procedures.
Numerous studies over the past twenty years have shown
that 100% of stomach and 95% of liver tumors are surface-
oriented outg rowths that are easily detected at gross nec-
ropsy [24, 26, 29]. From each organ having one or more sus-
pect tumors at necropsy, one slide was prepared for histol-
ogy. Tumor incidence is expressed as the percentage of fish
with one or more confirmed tumors per tank.
2.6 Statistical analysis
Logistic regression was used to compare tumor incidences
between treatment groups (Genmod procedure in SAS for
Windows version 9.1.3). There was no evidence of extrabi-
nomial variation between replicate tanks within treatment
groups (deviance/df a1, p A 0.47 for both liver and stom-
ach). Therefore, binomial variation was assumed and likeli-
hood ratio tests used to compare treatment groups. More
conservative tests (e.g. quasilikelihood t-tests using
observed tank-to-tank variation) would also indicate signif-
icant differences (p a 0.03 for both liver and stomach).
Exact two-sided rank tests (Kruskal-Wallis and Wil-
coxon) [30] were used to compare tumor multiplicity (per
gross tumor bearing animal) between treatment groups
(Npar1way procedure in SAS). There was no or little evi-
dence of differences between replicate tanks (p A 0.4 for
stomach in both treatment g roups, p A 0.14 for liver in both
treatment groups). Therefore, data were pooled over repli-
cate tanks and comparisons between treatment groups were
based on individual fish multiplicity. More conservative
tests (e.g. two-sided t-tests on tank means with 3 and 2
tanks per group) would give the same conclusions.
3 Results
Results of the acute toxicity studies with dietary tomatine
concentrations ranging from 100 to 2000 ppm show that
there were no significant differences in either the fish mor-
talities, body weights or the liver weights between groups
(Table 1). The livers of trout fed tomatine showed no gross
pathology. These observations suggest that tomatine at
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M. Friedman et al. Mol. Nutr. Food Res. 2007, 51, 1485 1491
70 mg/100 g wet weight is not acutely toxic to rainbow
trout.
Table 2 shows tumor incidences and tumor multiplicities
for both liver and stomach. Co-feeding tomatine and DBP
significantly reduced the incidence of liver tumors by
48.7% and the incidence of stomach tumors by 36.6% com-
pared to DBP alone (p = 0.01, p = 0.03 one-sided t-test),
respectively. Control treatments, OTD and tomatine,
showed no liver or stomach tumors.
Tumor multiplicity (total number of tumors per tank div-
ided by the number of tumor-bearing trout in the tank) in
the liver did not change significantly with the addition of
tomatine. However, Table 2 shows that stomach tumor mul-
tiplicity did drop significantly (p = 0.04, one-sided t-test).
Figure 2 depicts the change in stomach tumor multiplicity
by rank order. Of the tumor bearing trout fed only DBP,
24.7% had three to five tumors compared to 10% for those
co-fed DBP and tomatine. Of the tumor-bearing trout fed
DBP, 50.7% had only one tumor compared to 64.0% for
those co-fed DBP and tomatine. Independently, neither
change was statistically significant but the overall change
in stomach tumor multiplicity was.
4 Discussion
4.1 Anticarcinogenic effects of tomatine
This is the first report on the anticarcinogenic effects of
tomatine in vivo. Results of this initial study demonstrate
that a moderate dietary dose of 2000 ppm tomatine provides
anti-tumorigenic protection with potency similar to that
previously observed for chlorophyll [19], chlorophyllin
[18], and indole-3-carbinol [31] in the trout model. The
mechanism(s) of the anticarcinogenic effect of tomatine
remain to be investigated. Tomatine is known, however, to
bind to cholesterol in the digestive tract [9, 32], suggesting
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Table 1. Tomatine is not acutely toxic to trout in 4-week exposure
Group Mortality
a)
# Fish Average fish weight
(g) l SD
Average liver weight (g)
OTD (control diet) 0% 10 2.7 l 0.5 0.03
100 ppm tomatine 2% 10 3.0 l 0.8 0.03
500 ppm tomatine 0% 10 3.2 l 1.0 0.04
1000 ppm tomatine 2% 10 2.8 l1.1 0.03
2000 ppm tomatine 0% 10 2.9 l 1.1 0.02
a) Mortality is defined as the number of trout that died during the 4-week exposure divided by the number of trout per tank. The only
reported mortalities, 2%, were for the doses of 100 and 1000 ppm of tomatine.
Table 2. Tomatine-reduced liver tumor incidence, stomach tumor incidence and stomach tumor multiplicity in rainbow trout initiated
with dibenzo[a,l]pyrene
Treatment # Trout
per tank
Tumor incidence% Tumor multiplicity
a)
Liver Stomach Liver Stomach
DBP 224 ppm 96 32.2 52.1 1.6 1.8
98 37.8 45.9 2.1 1.8
95 41.1 41.1 2.0 2.1
Mean l SE 37.0 l 2.6 46.4 l 3.2 1.9 l 0.2 1.9 l 0.2
DBP 224 ppm 96 16.7 28.1 1.6 1.5
Tomatine 2000 ppm 75
b)
21.3 30.7 2.0 1.4
Mean l SE 19.0 l 2.3 29.4 l 1.5 1.8 l 0.2 1.5 l 0.1
p=a0.0001
c)
p = 0.0003
c)
p = 0.83
c)
p = 0.030
c)
% Reduction by tomatine 48.7 36.6 5.3 21.1
Controls
Oregon Test Diet 97 0 0
89 00––
Tomatine 2000 ppm 100 0 0
99 00––
a) Apparent tumor multiplicity was calculated by dividing the total number of grossly observed tumors in a tank by the total number
of tumor bearing fish in the tank. The endpoint is termed apparent tumor multiplicity because not every lesion in organs exhibiting
multiple lesions at gross necropsy was examined histologically.
b) Mortality due to human error in tank maintenance. Note tumor incidence for both liver and stomach are similar to the tank without
the loss.
c) p-value from asymptotic chi-square distribution.
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Mol. Nutr. Food Res. 2007, 51, 1485 1491
that its protective mechanism could be similar to those of
chlorophyll or chlorophyllin. Studies in trout and rats sug-
gest that non-covalent complexes formed between chloro-
phyll and chlorophyllin and carcinogens including aflatoxin
B1 [21, 22, 3335], DBP ([17, 18] and Simonich, M. T., et
al., submitted) and heterocyclic amines [20, 3638] are
poorly absorbed from the digestive tract, thus substantially
blocking initiation of chemical carcinogenesis. The more-
recent experiments show that this kind of protective mecha-
nism for chlorophylls extends to human volunteers (Bailey
et al., unpublished results). However, experiments analo-
gous to those mentioned above for chlorophyll (results not
shown) designed to find out whether tomatine binds to DBP
were negative. These observations suggest that the mecha-
nism of the tomatine effect probably differs from that pro-
posed for chlorophyll.
We suggest that the mechanism(s) of the chemo-preven-
tive effect of tomatine may be the result of multiple molec-
ular events including formation of complexes with choles-
terol [8], potentiation of the immune system [10], and direct
destruction of cancer cells via disruption of cell membranes
[11, 39, 40]. This latter process is initiated by binding
(intercalation) of tomatine to cholesterol located within cell
membranes [4, 41].
The bioavailability and in vitro binding of carcinogens by
both tomatine and dehydrotomatine require further study.
4.2 Relationship to tomato-based diets
Consumption of tomato products containing high levels of
lycopene [42] is reported to be associated with lowered can-
cer risk [43], including colorectal adenomas [44]. Tomato-
containing diets and lycopene also protected against N-
methyl-N-nitrosourea (NMU)-induced prostate cancer in a
rat model [45].
Our studies showed that the tomatine content of fresh
tomatoes is quite low, ranging from l4 to 42 mg/kg on a
dry weight basis [7]. By contrast, tomatine levels of green
tomatoes, including pickled green and fried green tomatoes
are 50 to 100 times higher than those of the standard red
varieties [7]. It is also relevant that red tomato varieties
grown in the mountains of Peru contain high levels of toma-
tine [46]. These considerations suggest that (i) reported
effects of red tomato-based diet against cancers and choles-
terol may at least be due in part to tomatine; (ii) it would be
of interest to ascertain whether high-tomatine green toma-
toes exhibit anticarcinogenic properties in vivo; and (iii)
there is a need to develop high-tomatine red tomatoes by
suppressing the genes in the tomato plant that govern the
formation of enzymes that degrade tomatine during post-
harvest ripening of tomatoes.
We especially thank Eric Johnson, Greg Gonnerman, and
Sheila Cleveland of the Sinnhuber Aquatic Research Labo-
ratory for their excellence in fish rearing, necropsy, and his-
tology. This work was partly supported through NIH grants
CA90890, ES00210, ES03850, and funds from the Linus
Pauling Institute at Oregon State University.
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    • "The male rats were randomly allocated in 10 groups (n = 10 per group) and treated for 8 week as follows: Group 1, control group: animals were treated intragastrically with solvent vehicle control (NaCl). Groups 2-4: animals were fed on tomatine, where tomatine over a range of doses (500, 1000, and 2000 ppm, respectively) was added to the oil component of the diet and fed daily for 8 weeks [29] [Friedmanet al., 2007]. Group 5, animals were treated intraperitoneal (i.p.) injection of KBrO 3 at a dose of 125mg/kg bodyweight [30] [Ke et al., 2013]. "
    [Show abstract] [Hide abstract] ABSTRACT: Abstract: Tomatine provides defence against pathogenic fungi, bacteria, viruses and herbivores. Therefore, evaluation the potential protective effects of dietary tomatine against gene expression alterations, oxidative DNA damage and suppression of antioxidant enzyme induced by potassium bromate- (KBrO3-) mediated oxidative stress in rats was studied. The effects of tomatine on gene expression alterations and DNA damage induced by KBrO3 were evaluated by quantitative Real Time-PCR and DNA laddering assay in liver cells. The effects of tomatine on the activities of GPx in liver cells were determined in male rats treated with KBrO3. Endogenous antioxidant status, namely, the activities GPx and the levels of GST-mRNA were significantly decreased in the liver tissues of the KBrO3-treated rats, while the pretreatment of tomatine prevented the decreases of these parameters induced by KBrO3 treatment. Moreover, the pretreatment of tomatine was also able to prevent KBrO3-induced increases in the expression levels of Hsp70a and CYP450 genes as well as DAN fragmentation in the liver tissues of male rats. Conclusion: The current results suggested that tomatine might act as a dietary protective agent with antioxidant properties offering effective protection against gene expression changes, oxidative DNA damage in a concentration-dependent manner in vivo. Keywords: Tomatine, KBrO3, Gene expression, DNA damage, rats. Introduction
    Full-text · Article · Jan 2015 · International Journal of PharmTech Research
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    • "Previous studies have reported its immunopotentiating [12] and in vitro anti-cancer activities [13,14,15,16]. It also has protective effects against dibenzo[a,l]pyrene (DBP)-induced liver and stomach tumors in rainbow trout without causing significant changes in total weight, liver weight, tissue morphology and mortality [17]. Thus far, the mechanism by which a-tomatine mediates its anti-prostate cancer effect is not well understood. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Nuclear factor-kappa B (NF-κB) plays a role in prostate cancer and agents that suppress its activation may inhibit development or progression of this malignancy. Alpha (α)-tomatine is the major saponin present in tomato (Lycopersicon esculentum) and we have previously reported that it suppresses tumor necrosis factor-alpha (TNF-α)-induced nuclear translocation of nuclear factor-kappa B (NF-κB) in androgen-independent prostate cancer PC-3 cells and also potently induces apoptosis of these cells. However, the precise mechanism by which α-tomatine suppresses NF-κB nuclear translocation is yet to be elucidated and the anti-tumor activity of this agent in vivo has not been examined. Methodology/principal findings: In the present study we show that suppression of NF-κB activation by α-tomatine occurs through inhibition of I kappa B alpha (IκBα) kinase activity, leading to sequential suppression of IκBα phosphorylation, IκBα degradation, NF-κB/p65 phosphorylation, and NF-κB p50/p65 nuclear translocation. Consistent with its ability to induce apoptosis, α-tomatine reduced TNF-α induced activation of the pro-survival mediator Akt and its inhibition of NF-κB activation was accompanied by significant reduction in the expression of NF-κB-dependent anti-apoptotic (c-IAP1, c-IAP2, Bcl-2, Bcl-xL, XIAP and survivin) proteins. We also evaluated the antitumor activity of α-tomatine against PC-3 cell tumors grown subcutaneously and orthotopically in mice. Our data indicate that intraperitoneal administration of α-tomatine significantly attenuates the growth of PC-3 cell tumors grown at both sites. Analysis of tumor material indicates that the tumor suppressing effects of α-tomatine were accompanied by increased apoptosis and lower proliferation of tumor cells as well as reduced nuclear translocation of the p50 and p65 components of NF-κB. Conclusion/significance: Our study provides first evidence for in vivo antitumor efficacy of α-tomatine against the human androgen-independent prostate cancer. The potential usefulness of α-tomatine in prostate cancer prevention and therapy requires further investigation.
    Full-text · Article · Feb 2013 · PLoS ONE
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    • "Both tomato and potato steroidal glycoalkaloids have antiproliferative effects against human cancer cell lines in vitro (Lee et al. 2004 ) and have also been shown to act as chemosensitisers, increasing the effectiveness of chemotherapeutic drugs by blocking their export through multi-drug resistance-type transport proteins (Lavie et al. 2001 ) . In addition, a -tomatine has recently been shown to protect fi sh against tumours induced by an environmental toxin (Friedman et al. 2007 ) . "
    [Show abstract] [Hide abstract] ABSTRACT: Saponins are one of the most numerous and diverse groups of plant natural products. They serve a range of ecological roles including plant defence against disease and herbivores and possibly as allelopathic agents in competitive interactions between plants. Some saponins are also important pharmaceuticals, and the underexplored biodiversity of plant saponins is likely to prove to be a vital resource for future drug discovery. The biological activity of saponins is normally attributed to the amphipathic properties of these molecules, which consist of a hydrophobic triterpene or sterol backbone and a hydrophilic carbohydrate chain, although some saponins are known to have potent biological activities that are dependent on other aspects of their structure. This chapter will focus on the biological activity and the synthesis of some of the best-studied examples of plant saponins and on recent developments in the identification of the genes and enzymes responsible for saponin synthesis.
    Full-text · Chapter · Jan 2013
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