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


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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    • "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]. "
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    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
    International Journal of PharmTech Research 01/2015;
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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 α-tomatine mediates its anti-prostate cancer effect is not well understood. "
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    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.
    PLoS ONE 02/2013; 8(2):e57708. DOI:10.1371/journal.pone.0057708 · 3.23 Impact Factor
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    • "It is also less cytotoxic against human liver normal cells and human prostate normal cells. Although our data showed that α-tomatine inhibited the growth of normal prostate RWPE-1 cells at high concentration (5.0 µM), where utilization of high dose of α-tomatine can be a key consideration for cancer treatment, earlier in vivo studies showed no apparent toxic effects in rainbow trout [19] and does not affect body and liver weights of mice [14], [27]. "
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    ABSTRACT: Alpha-tomatine (α-tomatine) is the major saponin in tomato (Lycopersicon esculentum). This study investigates the chemopreventive potential of α-tomatine on androgen-independent human prostatic adenocarcinoma PC-3 cells. Treatment of highly aggressive human prostate cancer PC-3 cells with α-tomatine resulted in a concentration-dependent inhibition of cell growth with a half-maximal efficient concentration (EC(50)) value of 1.67±0.3 µM. It is also less cytotoxic to normal human liver WRL-68 cells and normal human prostate RWPE-1 cells. Assessment of real-time growth kinetics by cell impedance-based Real-Time Cell Analyzer (RTCA) showed that α-tomatine exhibited its cytotoxic effects against PC-3 cells as early as an hour after treatment. The inhibitory effect of α-tomatine on PC-3 cancer cell growth was mainly due to induction of apoptosis as evidenced by positive Annexin V staining and decreased in mitochondrial membrane potential but increased in nuclear condensation, polarization of F-actin, cell membrane permeability and cytochrome c expressions. Results also showed that α-tomatine induced activation of caspase-3, -8 and -9, suggesting that both intrinsic and extrinsic apoptosis pathways are involved. Furthermore, nuclear factor-kappa B (NF-κB) nuclear translocation was inhibited, which in turn resulted in significant decreased in NF-κB/p50 and NF-κB/p65 in the nuclear fraction of the treated cells compared to the control untreated cells. These results provide further insights into the molecular mechanism of the anti-proliferative actions of α-tomatine. α-tomatine induces apoptosis and inhibits NF-κB activation on prostate cancer cells. These results suggest that α-tomatine may be beneficial for protection against prostate cancer development and progression.
    PLoS ONE 04/2011; 6(4):e18915. DOI:10.1371/journal.pone.0018915 · 3.23 Impact Factor
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