Chemoprevention of lung carcinogenesis by cacao liquor proanthocyanidins in a male rat multi-organ carcinogenesis model

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

doi:10.1016/s0304-3835(02)00629-8

Cited by 53 publications

(35 citation statements)

References 36 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: 86%

“…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: 86%

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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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“…Many in vitro experiments with pure PCs have shown antitumor-related activities but few have been confirmed in vivo [112][113][114][115][116][117]. PCs have been shown to inhibit TPA-mediated tumor promotion in the mouse epidermis [118,119].…”

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.

186

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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“…Cancer chemopreventive activity of cocoa has been reported that cocoa liquor procyanidins significantly reduced the incidence and multiplicity of lung carcinomas and also decreased thyroid adenomas developed in male rats [7]. Selected procyanidins present in cocoa inhibit tumorigenesis, tumor growth, and angiogenesis [8].…”

Section: Introductionmentioning

confidence: 99%

Anticancer Agents from Non-Edible Parts of Theobroma cacao

Zainal¹

2014

Nat Prod Chem Res 2014

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Chemoprevention of lung carcinogenesis by cacao liquor proanthocyanidins in a male rat multi-organ carcinogenesis model

Cited by 53 publications

References 36 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

Anticancer Agents from Non-Edible Parts of Theobroma cacao

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