Modulating effects of ellagic acid, vanillin and quercetin in a rat medium term multi-organ carcinogenesis model

Akagi, Keisuke; Hirose, Masao; Hoshiya, Toru; Mizoguchi, Yasumoto; Ito, Nobuyuki; Shirai, Tomoyuki

doi:10.1016/0304-3835(95)03833-i

Cited by 110 publications

(60 citation statements)

References 21 publications

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“…19 These findings were consistent with a previous report from Akagi et al 20 reporting that vanillin might increase the occurrence of colorectal cancer.…”

Section: Figsupporting

confidence: 90%

Vanillin Differentially Affects Azoxymethane-Injected Rat Colon Carcinogenesis and Gene Expression

Chong

Yazan

et al. 2012

Journal of Medicinal Food

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Vanillin is the substance responsible for the flavor and smell of vanilla, a widely used flavoring agent. Previous studies reported that vanillin is a good antimutagen and anticarcinogen. However, there are also some contradicting findings showing that vanillin was a comutagen and cocarcinogen. This study investigated whether vanillin is an anticarcinogen or a cocarcinogen in rats induced with azoxymethane (AOM). Rats induced with AOM will develop aberrant crypt foci (ACF). AOM-challenged rats were treated with vanillin orally and intraperitoneally at low and high concentrations and ACF density, multiplicity, and distribution were observed. The gene expression of 14 colorectal cancer-related genes was also studied. Results showed that vanillin consumed orally had no effect on ACF. However, high concentrations (300 mg/kg body weight) of vanillin administered through intraperitoneal injection could increase ACF density and ACF multiplicity. ACF were mainly found in the distal colon rather than in the mid-section and proximal colon. The expression of colorectal cancer biomarkers, protooncogenes, recombinational repair, mismatch repair, and cell cycle arrest, and tumor suppressor gene expression were also affected by vanillin. Vanillin was not cocarcinogenic when consumed orally. However, it was cocarcinogenic when being administered intraperitoneally at high concentration. Hence, the use of vanillin in food should be safe but might have cocarcinogenic potential when it is used in high concentration for therapeutic purposes.

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“…19 These findings were consistent with a previous report from Akagi et al 20 reporting that vanillin might increase the occurrence of colorectal cancer.…”

Section: Figsupporting

confidence: 90%

Vanillin Differentially Affects Azoxymethane-Injected Rat Colon Carcinogenesis and Gene Expression

Chong

Yazan

et al. 2012

Journal of Medicinal Food

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“…It exhibits the anticancer potential by the regulations of cell cycle and apoptosis in HepG2 cells (Cheng et al, 2007). It also possesses the chemopreventive effect in multiorgan carcinogenesis and hepatocarcinogenesis models in rats (Akagi et al, 1995). In this study, we demonstrated that vanillin inhibits MMP-9 expression, resulting in the inhibition of HepG2 cell invasion.…”

Section: Discussionmentioning

confidence: 56%

“…Vanillin inhibits chemical and physical mutagens-induced mutagenesis in both bacteria and mammalian cells (Keshava et al, 1998;Shaughnessy et al, 2006). It also displays chemopreventive effects in multiorgan carcinogenesis and hepatocarcinogenesis models in rats (Akagi et al, 1995).…”

mentioning

confidence: 99%

Vanillin Inhibits Matrix Metalloproteinase-9 Expression through Down-Regulation of Nuclear Factor-κB Signaling Pathway in Human Hepatocellular Carcinoma Cells

Liang

et al. 2008

Mol Pharmacol

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Vanillin has been reported to exhibit anti-invasive and antimetastatic activities by suppressing the enzymatic activity of matrix metalloproteinase-9 (MMP-9). However, the underlying mechanism of anti-invasive activity remains unclear so far. Herein we demonstrate that vanillin reduced 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 gelatinolytic activity and suppressed cell invasion through the down-regulation of MMP-9 gene transcription in HepG2 cells. Vanillin significantly reduced the 6.6-fold invasive capacity of HepG2 cells in noncytotoxic concentrations, and this anti-invasive effect was concentration-dependent in the Matrigel invasion assay. Moreover, vanillin significantly suppressed the TPA-induced enzymatic activity of MMP-9 and decreased the induced mRNA level of MMP-9. Analysis of the transcriptional regulation indicated that vanillin suppressed MMP-9 transcription by inhibiting nuclear factor-B (NF-B) activity. Western blot further confirmed that vanillin inhibited NF-B activity through the inhibition of IB-␣ phosphorylation and degradation. In conclusion, vanillin might be a potent antiinvasive agent that suppresses the MMP-9 enzymatic activity via NF-B signaling pathway.

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“…), s.c. injections of 1,2-dimethylhydrazine (DMH, 40 mg/kg body wt. ), and 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) and 0.1% 2,2'-dihydroxy-di-npropylnitrosamine (DHPN), both in the drinking water, for a total initiation period of 4 weeks (DMBDD treatment) (Akagi et al 1995;Ito et al 1996). Then rats are given the test compound in the diet or drinking water or by injection for the following 24 weeks.…”

Section: Ito Multi-organ Model (Dmbdd Model)mentioning

confidence: 99%

A Medium-Term, Rapid Rat Bioassay Model for the Detection of Carcinogenic Potential of Chemicals

et al. 2010

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The Ito Liver Model and the Ito Multi-organ Model are used in conjunction and constitute an efficient and rapid bioassay for the identification of both genotoxic and nongenotoxic carcinogenic chemicals. The Ito Liver Model is an 8-week bioassay system that uses the number and size of foci of hepatocytes positive for glutathione S-transferase placental form (GST-P) as the end-point marker. One hundred fifty-nine compounds were tested using the Ito Liver Model: 61 of 66 hepatocarcinogens tested positive, and 10 of 43 nonliver carcinogens were also positive. The false-positive detection of noncarcinogens was low; a single false-positive result was obtained from the 50 noncarcinogens tested. Since more than half of all known carcinogens are hepatocarcinogens in rodents, the initial 8-week bioassay is able to detect most carcinogens. The Ito Multi-organ Model is a 28-week bioassay system for the detection of carcinogens that were not identified by the Ito Liver Model. Results are evaluated by preneoplastic and neoplastic lesions in major organs. Forty-four compounds were tested using the Ito Multi-organ Model: 17 out of 17 liver carcinogens were positive, and 19 out of 22 (86%) nonliver carcinogens were positive. None of the five noncarcinogens tested positive.

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Modulating effects of ellagic acid, vanillin and quercetin in a rat medium term multi-organ carcinogenesis model

Cited by 110 publications

References 21 publications

Vanillin Differentially Affects Azoxymethane-Injected Rat Colon Carcinogenesis and Gene Expression

Vanillin Differentially Affects Azoxymethane-Injected Rat Colon Carcinogenesis and Gene Expression

Vanillin Inhibits Matrix Metalloproteinase-9 Expression through Down-Regulation of Nuclear Factor-κB Signaling Pathway in Human Hepatocellular Carcinoma Cells

A Medium-Term, Rapid Rat Bioassay Model for the Detection of Carcinogenic Potential of Chemicals

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