Chemoprevention of DMBA-induced mammary carcinogenesis in rats by low-dose EPA and DHA

Noguchi, Masakuni; Minami, Masaki; Yagasaki, Ryo; Kinoshita, Kazuo; Earashi, Mitsuharu; Kitagawa, Hirohisa; Taniya, Takao; Miyazaki, Itsuo

doi:10.1038/bjc.1997.57

Cited by 86 publications

(51 citation statements)

References 29 publications

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“…Tamoxifen reduced cancer incidence, cancer multiplicity, and cancer burden in the absence of any effect of the n-3:n-6 ratio (Table 3). This finding, although consistent with the mammary gland density data (Table 2) and the null findings reported in references 12, 36, and 38, disagrees with other published reports in which high levels of dietary fish oil were reported to protect against chemically induced mammary carcinogenesis (10)(11)(12)(13)(14)(15)(16)(17)(18).…”

Section: Discussionsupporting

confidence: 78%

“…Moreover, the preclinical data on the role of n-3 fatty acids in mammary carcinogenesis is similarly mixed (inhibition, no effect, or promotion of carcinogenesis), and the quality of the experiments varies so markedly that it is difficult to compare results across studies (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). These circumstances prompted the work reported herein.…”

Section: Introductionmentioning

confidence: 99%

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Mammary Gland Density Predicts the Cancer Inhibitory Activity of the N-3 to N-6 Ratio of Dietary Fat

Zhu

Jiang

McGinley

et al. 2011

Cancer Prevention Research

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This study investigated the effect of a broad range of dietary ratios of n-3:n-6 fatty acids on mammary gland density and mammary cancer risk. Cancer was induced in female rats by N-methyl-N-nitrosourea. Purified diet that provided 30% of dietary kilocalories from fat was formulated to contain ratios of n-3:n-6 fatty acids from 25:1 to 1:25. Mammary gland density was determined by digital analysis, fatty acids by gas chromatography/flame ionization detection, and other plasma analytes via ELISA. Mammary gland density was reduced dose dependently at n-3:n-6 ratios from 1:1 to 25:1 (r ¼ À0.477, P ¼ 0.038), with a 20.3% decrease of mammary gland density between n-3:n-6 of 1:1 versus 25:1, P < 0.001. Mammary carcinogenesis was inhibited in the absence or presence of tamoxifen (1 mg/kg diet) in a manner predicted by mammary gland density. Plasma n-3 fatty acid concentrations failed to increase above an n-3:n-6 ratio of 5:1, and changes in specific plasma n-3 or n-6 fatty acids were not predictive of mammary gland density or cancer inhibitory activity. A strong reciprocal effect of the n-3:n-6 ratio on plasma leptin (decreased, P ¼ 0.005) and adiponectin (increased, P < 0.001) was observed indicating adipose tissue function was modulated. However, neither cytokine was predictive of mammary gland density. Plasma insulin-like growth factor I (IGF-I) decreased with increasing dietary n-3:n-6 ratio (P ¼ 0.004) and was predictive of the changes in mammary gland density (r ¼ 0.362, P < 0.005). These findings indicate that (i) mammary gland density predicted the carcinogenic response, (ii) the n-3:n-6 ratio exerts effects in the presence or absence of hormonal regulation of carcinogenesis, and (iii) signaling pathways regulated by IGF-I are potential targets for further mechanistic investigation. Cancer Prev Res; 4(10); 1675-85. Ó2011 AACR.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Mammary Gland Density Predicts the Cancer Inhibitory Activity of the N-3 to N-6 Ratio of Dietary Fat

Zhu

Jiang

McGinley

et al. 2011

Cancer Prevention Research

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“…It has been postulated that the risk of breast cancer can be influenced by certain dietary components such as the amount and type of dietary fats ingested (3)(4)(5)(6)(7). Among the fatty acids, omega-3 (n-3) and omega-6 (n-6) fatty acids have been suggested to decrease and increase breast cancer risk, respectively.…”

Section: Introductionmentioning

confidence: 99%

Proteomic Changes Induced by Effective Chemopreventive Ratios of n-3:n-6 Fatty Acids and Tamoxifen against MNU-Induced Mammary Cancer in the Rat

Skibinski

Thompson

Das

et al. 2013

Cancer Prevention Research

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We used a proteomic approach to gain insights into the mechanisms of protection at the protein level by a high n-3:n-6 ratio in the absence and presence of Tamoxifen. Four groups were treated with 1-methyl-1-nitrosourea (MNU) and fed the following diets with varied n-3:n-6 ratios; group 1 ¼ 1:1; groups 2 and 3 ¼ 10:1 and 25:1, respectively; group 4: (25:1) plus Tamoxifen (1 mg/kg diet). The plasma from six rats/group was pooled and analyzed with the isobaric tags for relative and absolute quantitation method; 148 proteins were identified with 95% confidence by ProteinPilot 4.0. In plasma of rats fed 10:1, 25:1 n-3:n-6, and 25:1 plus Tamoxifen, the number of proteins that met our criteria (P 0.05, error factor 2) were 10, 14, and 19 proteins, respectively. Selected proteins were further validated by Western blotting. Compared to 1:1, both 10:1 and 25:1 diets upregulated vitamin D binding protein, gelsolin, and 14-3-3 sigma, reported to have tumor suppressive effects, whereas alpha-1B-glycoprotein, which has been reported to be elevated in the serum of breast cancer patients was decreased. Compared to 25:1, the 25:1 plus Tamoxifen diet downregulated apolipoprotein E, haptoglobin, and inter-a-inhibitor H4 heavy chain. Ingenuity pathway analysis determined that the trends of specific proteins were related to lipid metabolism in the 25:1 n-3:n-6 group, whereas the 25:1 n-3:n-6 plus Tamoxifen group included proteins involved in cancer and inflammation. Our results show that several proteins were altered in a manner consistent with chemoprevention. Such proteins may serve as biomarkers to monitor efficacy of n-3 and Tamoxifen in future clinical chemoprevention trials. Cancer Prev Res; 6(9); 979-88. Ó2013 AACR.

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“…Both epidemiologic and experimental studies have suggested that n-3 PUFAs can exert a chemopreventive effect against some common tumours and multiple mechanisms have been involved in this activity, including suppression of neoplastic transformation (Noguchi et al, 1997), cell cycle arrest (Albino et al, 2000), induction of apoptosis (Latham et al, 1999), antiangiogenesis and suppression of metastasis Senzaki et al, 1998). This study was designed to assess the possible interaction of n-3 PUFAs and ionising radiation, which has not been reported before.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple mechanisms are involved in this chemopreventive activity, including suppression of neoplastic transformation (Noguchi et al, 1997), cell cycle arrest (Albino et al, 2000), induction of apoptosis (Latham et al, 1999), antiangiogenesis and suppression of metastasis (Suzuki et al, 1997;Senzaki et al, 1998). However, a common feature of most biological effects is the inhibition of eicosanoid production from n-6 fatty acid precursors.…”

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confidence: 99%

n-3 Polyunsaturated fatty acids decrease mucosal/epidermal reactions and enhance antitumour effect of ionising radiation with inhibition of tumour angiogenesis

et al. 2003

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The purpose of this study was to evaluate the effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) on normal tissue (lip mucosa) and tumour growth when combined with ionising radiation. The oral region (snout) of C57 black mice was irradiated with 16.5 Gy and n-3 PUFAs (100 ml) were injected intravenously for 2 weeks. After exposure to irradiation, the degree and duration of the acute reactions decreased significantly when mice were treated with n-3 PUFAs as compared to the control group. Interestingly, the range of the reactions in the n-3 PUFAs-treated group compared favourably to the group receiving amifostine (27.5 mg/kg i.v.). the effect of n-3 PUFAs was further evaluated in HEP-2 human carcinoma xenograft transplanted in nude mice. An inhibition of tumour growth was observed when mice were treated with n-3 PUFAs alone and this effect was maximal when combined with irradiation. Similar results were obtained using eicosapentaenoic acid. The effect of n-3 PUFAs was associated with inhibition of angiogenesis and tumour proliferation, and significantly decreased expression of cyclooxygenase-2. In conclusion, n-3 PUFAs administration decrease mucosal response, while moderately enhancing the antitumour effect of irradiation. The magnitude of the differential effect suggests that n-3 PUFAs need to be further investigated in the clinic.

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Chemoprevention of DMBA-induced mammary carcinogenesis in rats by low-dose EPA and DHA

Cited by 86 publications

References 29 publications

Mammary Gland Density Predicts the Cancer Inhibitory Activity of the N-3 to N-6 Ratio of Dietary Fat

Mammary Gland Density Predicts the Cancer Inhibitory Activity of the N-3 to N-6 Ratio of Dietary Fat

Proteomic Changes Induced by Effective Chemopreventive Ratios of n-3:n-6 Fatty Acids and Tamoxifen against MNU-Induced Mammary Cancer in the Rat

n-3 Polyunsaturated fatty acids decrease mucosal/epidermal reactions and enhance antitumour effect of ionising radiation with inhibition of tumour angiogenesis

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