Effects of cacao liquor proanthocyanidins on PhIP-induced mutagenesis in vitro, and in vivo mammary and pancreatic tumorigenesis in female Sprague–Dawley rats

Yamagishi, Megumi; Natsume, Mitsutaka; Osakabe, Naomi; Nakamura, Hideaki; Furukawa, Fumio; Imazawa, Takayoshi; Nishikawa, Akiyoshi; Hirose, Masao

doi:10.1016/s0304-3835(02)00276-8

Cited by 48 publications

(34 citation statements)

References 41 publications

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“…Our previous studies demonstrated that cocoa extracts protected against oxidative stress-induced inhibition of gap-junction intercellular communication (33) and TPA-induced COX-2 protein expression in mouse skin (34). Moreover, recent studies have shown that orally administered cocoa powder or cocoa liquor inhibits chemically induced carcinogenesis in experimental animals (9,10). Our results, therefore, support the chemopreventive potential of cocoa procyanidins.…”

Section: Discussionsupporting

confidence: 87%

“…Therefore, cocoa beans contain much less theobromine than procyanidins. Accumulated data provide evidence that the consumption of cocoa or dark chocolate can decrease the burden and efficacy of epigenetic carcinogens (9,10). However, the underlying molecular mechanisms and molecular target(s) for the potential chemopreventive effects of cocoa and its active ingredient(s) remain unknown.…”

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confidence: 99%

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Cocoa Procyanidins Suppress Transformation by Inhibiting Mitogen-activated Protein Kinase Kinase

Kang

Lee

et al. 2008

Journal of Biological Chemistry

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Cocoa was shown to inhibit chemically induced carcinogenesis in animals and exert antioxidant activity in humans. However, the molecular mechanisms of the chemopreventive potential of cocoa and its active ingredient(s) remain unknown. Here we report that cocoa procyanidins inhibit neoplastic cell transformation by suppressing the kinase activity of mitogen-activated protein kinase kinase (MEK). A cocoa procyanidin fraction (CPF) and procyanidin B2 at 5 g/ml and 40 M, respectively, inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic transformation of JB6 P؉ mouse epidermal (JB6 P؉) cells by 47 and 93%, respectively. The TPAinduced promoter activity and expression of cyclooxygenase-2, which is involved in tumor promotion and inflammation, were dose-dependently inhibited by CPF or procyanidin B2. The activation of activator protein-1 and nuclear factor-B induced by TPA was also attenuated by CPF or procyanidin B2. The TPAinduced phosphorylation of MEK, extracellular signal-regulated kinase, and p90 ribosomal s6 kinase was suppressed by CPF or procyanidin B2. In vitro and ex vivo kinase assay data demonstrated that CPF or procyanidin B2 inhibited the kinase activity of MEK1 and directly bound with MEK1. CPF or procyanidin B2 suppressed JB6 P؉ cell transformation induced by epidermal growth factor or H-Ras, both of which are known to be involved in MEK/ERK signal activation. In contrast, theobromine (up to 80 M) had no effect on TPA-induced transformation, cyclooxygenase-2 expression, the transactivation of activator protein-1 or nuclear factor-B, or MEK. Notably, procyanidin B2 exerted stronger inhibitory effects compared with PD098059 (a well known pharmacological inhibitor of MEK) on MEK1 activity and neoplastic cell transformation.

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Section: Discussionsupporting

confidence: 87%

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confidence: 99%

Cocoa Procyanidins Suppress Transformation by Inhibiting Mitogen-activated Protein Kinase Kinase

Kang

Lee

et al. 2008

Journal of Biological Chemistry

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“…PCs have been shown to inhibit TPA-mediated tumor promotion in the mouse epidermis [118,119]. Cocoa liquor PCs have also been shown to inhibit rat pancreatic carcinogenesis at the initiation stage as well as lung carcinogenesis in a rat multi-organ carcinogenesis model [117,120]. A protective role of PCs against cardiovascular diseases has been suggested by many experimental studies, which have shown induction of endothelium-dependent relaxation via activation of nitric oxide synthase [121], enhancement of prostacyclin release [122][123][124], inhibition of oxidative modification of low-density lipoprotein [125][126][127], and inhibition of platelet aggregation [61,128].…”

Section: Biological Effects Of Pcsmentioning

confidence: 99%

Bioavailability issues in studying the health effects of plant polyphenolic compounds

Yang¹,

Sang

Lambert

et al. 2008

Mol. Nutr. Food Res.

184

209

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Polyphenolic compounds are common in the diet and have been suggested to have a number of beneficial health effects including prevention of cancer, cardiovascular disease, diabetes, and others. For some dietary polyphenols, certain benficial effects are suggested by epidemiological studies, some are supported by studies in animal models, and still others are extrapolated from studies in vitro. Because of the relatively poor bioavailability of many of these compounds, the molecular basis of these beneficial effects is not clear. In the present review, we discuss the potential health benefits of dietary polyphenols from the point of view of bioavailability. Tea catechins, curcumin, and proanthocyanidins are used as examples to illustrate some of the problems that need to be resolved. Further research on both the biological activity and bioavailability of dietary polyphenols is needed to properly assess their usefulness for the prevention and treatment of disease.

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“…In addition to antioxidative action 10 , anthocyanins including cyanidine have been shown to exert anti-tumoral effects in vitro [17][18][19][20] . Recently, it was found that proanthocyanidine, a polyphenol contained in cacao, can inhibit the in vitro or ex vivo mutagenicity of PhIP 21 as well as other HCAs…”

Section: Discussionmentioning

confidence: 99%

“…In fact, cacao liquor polyphenols were earlier found to inhibit pancreatic carcinogenesis in rats receiving PhIP 21 and lung carcinogenesis in a rat multi-organ model 23 . In the present study, except for a slight but dosedependent decrease of PhIP-DNA adduct formation in the pancreas, acetoside affected neither DNA adduct formation nor BrdU-labeling in the three target organs investigated.…”

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confidence: 99%

Rapid Screening for Chemopreventive Agents in Herbal Extracts in a PhIP Rat Model with DNA Adduct and Cell Proliferation as End-Points

et al. 2007

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This study was designed to rapidly screen for chemopreventive effects of three natural products, cyanidine-3-glycoside, acetoside and rosemaric acid, against 2-amino-1-methyl-6-phenyl-imidazo [4,5-b]pyridine (PhIP)-induced colonic, pancreatic and prostatic carcinogenesis in rats, using DNA adduct and cell proliferation as end-points. Tenweek-old F344 male rats were maintained for 2 weeks on a powdered basal diet containing 0.03% PhIP alone, PhIP together with 1% or 5% cyanidine-3-glycoside, acetoside or rosemaric acid, 1% or 5% cyanidine-3-glycoside, acetoside or rosemaric acid alone or basal diet. Immunohistochemically, PhIP DNA adduct-positive cells as well as BrdU-positive cells induced by PhIP treatment were significantly (P<0.05) reduced by the combined treatment with 5% cyanidine-3-glycoside in the proximal colon and pancreatic acinar cells as compared to the PhIP alone group values. In addition, combined treatment with 5% cyanidine-3-glycoside significantly (P<0.05) decreased numbers of BrdU-positive cells in the ventral prostate. Combined treatment with 5% rosemaric acid also significantly (P<0.05) reduced PhIP DNA adductpositive cells in the proximal and distal colon, and ventral prostate as well as BrdU-positive cells in the lateral prostate and exocrine pancreas at 5%, and in the distal colon with 1% or 5%. However, co-treatment with acetoside did not significantly affect these parameters under the present experimental conditions. These results suggest that cyanidine-3-glycoside and rosemaric acid may have the potential to prevent PhIP-induced carcinogenesis in the colon, prostate and/ or pancreas. (J Toxicol Pathol 2007; 20: 49-54)

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Effects of cacao liquor proanthocyanidins on PhIP-induced mutagenesis in vitro, and in vivo mammary and pancreatic tumorigenesis in female Sprague–Dawley rats

Cited by 48 publications

References 41 publications

Cocoa Procyanidins Suppress Transformation by Inhibiting Mitogen-activated Protein Kinase Kinase

Cocoa Procyanidins Suppress Transformation by Inhibiting Mitogen-activated Protein Kinase Kinase

Bioavailability issues in studying the health effects of plant polyphenolic compounds

Rapid Screening for Chemopreventive Agents in Herbal Extracts in a PhIP Rat Model with DNA Adduct and Cell Proliferation as End-Points

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