Inhibition of Azoxymethane Initiated Colon Tumor and Aberrant Crypt Foci Development by Bovine Lactoferrin Administration in F344 Rats

Tsuda, Hiroyuki; Sekine, Kazunori; Nakamura, Joe; Ushida, Yoshihiko; Kuhara, Tetsuya; Takasuka, Nobuo; Kim, Dae Joong; Asamoto, Makoto; Baba-Toriyama, Hiroyasu; Moore, Malcolm A; Nishino, Hoyoku; Kakizoe, Tadao

doi:10.1007/978-1-4757-9068-9_34

Cited by 55 publications

(40 citation statements)

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“…These findings indicate no toxicity of bLF, as reported in previous studies. [25][26][27][28] This is important for the possible application of this cancer chemopreventive compound in human clinical trials, because such trials require long-term oral administration of tested compounds.…”

Section: Discussionmentioning

confidence: 99%

“…[21][22][23] Among them, the anti-bacterial action of LF is considered to be caused through sequestra-tion of iron required for microbial growth. 24) Recently, chemopreventive ability of bovine LF (bLF) was demonstrated in chemically induced carcinogenesis in colon, [25][26][27] esophagus 28) and lung. 28) bLF could also inhibit intestinal polyposis in Apc Min mice.…”

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confidence: 99%

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Chemopreventive Effect of Bovine Lactoferrin on 4‐Nitroquinoline 1‐Oxide‐induced Tongue Carcinogenesis in Male F344 Rats

Tanaka

Kawabata

Kohno

et al. 2000

Japanese Journal of Cancer Research

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The modifying effects of dietary feeding of bovine lactoferrin (bLF) on tongue carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. The activities of phase II detoxifying enzymes, glutathione S-transferase (GST) and quinone reductase (QR), polyamine content and ornithine decarboxylase (ODC) activity in the tongue were also examined for mechanistic analysis of possible modifying effects of bLF on carcinogenesis. At 7 weeks of age, all animals except those treated with bLF alone and untreated rats were given 20 ppm 4-NQO in drinking water for 8 weeks to induce tongue neoplasms. Starting 7 days before 4-NQO exposure, experimental groups were fed experimental diets containing bLF (0.2% and 2%) for 10 weeks ("initiation feeding"). Starting 1 week after the cessation of exposure to 4-NQO, the other experimental groups given 4-NQO and a basal diet were fed the experimental diets for 22 weeks ("postinitiation feeding"). At week 32, the incidence and multiplicity of tongue neoplasms in the "initiation feeding" groups of 0.2% and 2% bLF and the "post-initiation feeding" group of 0.2% bLF were lower than those of the 4-NQO alone group, but without statistical significance. However, "post-initiation feeding" of 2% bLF caused a significant reduction in the incidence (20% vs. 55%, P = = = =0.02418) and multiplicity (0.25± ± ± ±0.54 vs. 0.70 ± ± ± ±0.71, P< < < <0.05) of tongue squamous cell carcinoma (by 64%, P = = = =0.02418). bLF treatment elevated liver and tongue GST activities and liver QR activity. The "post-initiation feeding" with 2% bLF significantly decreased QR activity, proliferating cell nulcear antigen-positive index and ODC activity in the tongue. In addition, feeding with bLF decreased tongue polyamine content. These results suggest that bLF, when given at the 2% dose level during the post-initiation phase, exerts chemopreventive action against tongue tumorigenesis through modification of cell proliferation activity and/or the activities of detoxifying enzymes.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Chemopreventive Effect of Bovine Lactoferrin on 4‐Nitroquinoline 1‐Oxide‐induced Tongue Carcinogenesis in Male F344 Rats

Tanaka

Kawabata

Kohno

et al. 2000

Japanese Journal of Cancer Research

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“…In addition, intratumoral injections of LfcinB slow the growth of murine Meth A fibrosarcoma cells grown as s.c. tumors in mice (8). Furthermore, oral administration of LfcinB to rats that had been injected previously with azoxymethane to promote colon carcinogenesis results in an impressive 83% reduction in the incidence of colon adenocarcinomas (7). A similar effect was achieved by oral administration of intact bovine lactoferrin, which raises the intriguing possibility that LfcinB derived from dietary bovine lactoferrin may protect against colon carcinogenesis.…”

Section: Introductionmentioning

confidence: 95%

Bovine lactoferricin selectively induces apoptosis in human leukemia and carcinoma cell lines

Mader

Salsman²,

Conrad³

et al. 2005

Molecular Cancer Therapeutics

234

180

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Bovine lactoferricin (LfcinB) is a cationic, amphipathic peptide that is cytotoxic for human and rodent cancer cells. However, the mechanism by which LfcinB causes the death of cancer cells is not well understood. Here, we show that in vitro treatment with LfcinB rapidly induced apoptosis in several different human leukemia and carcinoma cell lines as determined by DNA fragmentation assays and phosphatidylserine headgroup inversion detected by Annexin V binding to the surface of cancer cells. Importantly, LfcinB treatment did not adversely affect the viability of untransformed human lymphocytes, fibroblasts, or endothelial cells. Studies with different LfcinB-derived peptide fragments revealed that the cytotoxic activity of LfcinB resided within the amino acid sequence FKCRRWQWRM. Treatment of Jurkat T leukemia cells with LfcinB resulted in the production of reactive oxygen species followed by caspase-2-induced dissipation of mitochondrial transmembrane potential and subsequent activation of caspase-9 and caspase-3. Selective inhibitors of caspase-2 (Z-VDVAD-FMK), caspase-9 (Z-LEHD-FMK), and caspase-3 (Z-DEVD-FMK) protected both leukemia and carcinoma cells from LfcinB-induced apoptosis. Conversely, a caspase-8 inhibitor (Z-IETD-FMK) had no effect, which argued against a role for caspase-8 and was consistent with the finding that death receptors were not involved in LfcinB-induced apoptosis. Furthermore, Jurkat T leukemia cells that overexpressed Bcl-2 were less sensitive to LfcinB-induced apoptosis, which was characterized by mitochondrial swelling and the release of cytochrome c from mitochondria into the cytosolic compartment. We conclude that LfcinB kills cancer cells by triggering the mitochondrial pathway of apoptosis at least in part through the generation of reactive oxygen species. [Mol Cancer Ther 2005;4(4):612 -24]

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“…Since ACF are considered to be putative precursor lesions of colon cancer (4), they have been proposed as useful biomarkers for a screening assay of chemopreventive agents for colon cancer (45,47). In this study, we administered C. butyricum spores as probiotics to rats and fed the rats a diet of HAS as prebiotics to increase production of SCFA in the large intestine, expecting that they would show inhibitory effects on AOM-induced formation of ACF.…”

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confidence: 99%

Effects of High Amylose Maize Starch and Clostridium butyricum on Metabolism in Colonic Microbiota and Formation of Azoxymethane‐Induced Aberrant Crypt Foci in the Rat Colon

Nakanishi

Kataoka

Kuwahara

et al. 2003

Microbiology and Immunology

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High amylose maize starch (HAS) is not digested in the small intestine and most of it reaches the large intestine. In the large intestine, HAS is fermented by intestinal bacteria, resulting in production of short‐chain fatty acids (SCFA), particularly butyrate. Clostridium butyricum can utilize HAS and produce butyrate and acetate. It has been proposed that butyrate inhibits carcinogenesis in the colon. In this study, we examined the inhibitory effects of HAS and C. butyricum strain MIYAIRI588 (CBM588) on azoxymethane‐induced aberrant crypt foci (ACF) formation in rats. In the group of rats administered only CBM588 spores, the concentration of butyrate in the cecum increased, but there was no decrease in the number of ACF. In the group of rats fed an HAS diet, a decrease in the number of ACF was observed, and in the group of rats administered HAS and CBM588, the number of ACF decreased significantly. In these two groups, the concentrations of acetate and propionate in intestinal contents significantly increased, but the concentration of butyrate did not change. It was found that the β‐glucuronidase activity level of colonic contents decreased significantly in the two groups of rats fed HAS. This study showed that HAS and CBM588 changed the metabolism of colonic microbiota and decreased the level of β‐glucuronidase activity, phenomena that may play a role in the inhibition of ACF formation in the rat colon.

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Inhibition of Azoxymethane Initiated Colon Tumor and Aberrant Crypt Foci Development by Bovine Lactoferrin Administration in F344 Rats

Cited by 55 publications

References 20 publications

Chemopreventive Effect of Bovine Lactoferrin on 4‐Nitroquinoline 1‐Oxide‐induced Tongue Carcinogenesis in Male F344 Rats

Chemopreventive Effect of Bovine Lactoferrin on 4‐Nitroquinoline 1‐Oxide‐induced Tongue Carcinogenesis in Male F344 Rats

Bovine lactoferricin selectively induces apoptosis in human leukemia and carcinoma cell lines

Effects of High Amylose Maize Starch and Clostridium butyricum on Metabolism in Colonic Microbiota and Formation of Azoxymethane‐Induced Aberrant Crypt Foci in the Rat Colon

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