Possible Chemopreventive Effects of Bovine Lactoferrin on Esophagus and Lung Carcinogenesis in the Rat

Ushida, Yoshihiko; Sekine, Kazunori; Kuhara, Tetsuya; Takasuka, Nobuo; Iigo, Masaaki; Maeda, Mitsuaki; Tsuda, Hiroyuki

doi:10.1111/j.1349-7006.1999.tb00742.x

Cited by 76 publications

(54 citation statements)

References 18 publications

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“…[17][18][19][20] Interestingly, in experimental studies, lactoferrin has been shown to inhibit the growth of some solid tumors such as colon, esophagus, and lung tumors. 21,22 Interestingly, stool lactoferrin has been shown to be a sensitive marker of intestinal inflammation in patients with intestinal tract symptoms and is being used in clinical practice to identify patients with intestinal tract inflammation. 23 Our results suggest that the detection of lactoferrin protein levels in the stool might also be a practical noninvasive screening test for pancreatic inflammation or cancer invasion among patients with suspected pancreatic disease.…”

Section: Discussionmentioning

confidence: 99%

Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma

et al. 2005

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The non-neoplastic pancreatic parenchyma adjacent to infiltrating ductal adenocarcinoma demonstrates inflammation, fibrosis, acinar cell loss and small duct-like metaplasia of acinar cells. Similar morphologic changes are also observed in the setting of chronic pancreatitis. In addition, peritumoral acini have been shown to have alterations in gene expression even in the absence of morphological changes. To better understand the pancreatic acinar responses to infiltrating pancreatic ductal adenocarcinoma, we characterized gene expression patterns of pancreatic acinar tissue adjacent to infiltrating pancreatic ductal adenocarcinomas and compared them to gene expression patterns of acinar tissue affected by chronic pancreatitis as well as to those of normal pancreatic acini. Fresh-frozen pancreatic acinar tissue was microdissected from nine patients (three with pancreatic cancer, three with chronic pancreatitis, three with normal pancreata) using laser capture microdissection, and extracted RNA from each microdissection was subjected to two rounds of linear amplification and hybridized to oligonucleotide microarrays. Gene expression patterns were confirmed using quantitative RT-PCR and/or immunohistochemistry. A total of 20 genes was found to be overexpressed in peritumoral acinar tissue compared to normal acinar tissue and to acini affected by chronic pancreatitis. These 20 genes included pancreatitis-associated protein (HIP/PAP), a gene known to be overexpressed in acini adjacent to infiltrating pancreatic cancer, and the gene cartilage glycoprotein-39 (HC gp-39 or TKL-40). Serum HC gp-39 protein levels were significantly higher in patients with pancreatic cancer and in those with chronic pancreatitis than in controls without pancreatic disease. There was no significant difference in the levels of serum HC gp-39 in patients with pancreatic cancer and those with chronic pancreatitis. Our results demonstrate some of the molecular alterations in acinar cells that occur in response to adjacent infiltrating pancreatic ductal adenocarcinoma and reveal that such alterations can provide a rich source of markers of pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma

et al. 2005

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“…Lfn-p induces apoptotic cell death in the human oral squamous cell carcinoma cell line SAS Lfn and a pepsin-digested lactoferrin peptide, Lfc, have been reported to inhibit tumor cell growth and induce cell death (7,8). We examined whether Lfn-p induces cell death in the oral squamous cell carcinoma cell line SAS.…”

Section: Resultsmentioning

confidence: 99%

“…Lfc B from bovine Lfn induces cell death in a human leukemia cell line and in endocervix adenocarcinomas and breast cancers (7,8). Lfn is progressively down-regulated in neoplastic transformation (32).…”

Section: Discussionmentioning

confidence: 99%

Pepsin-Digested Bovine Lactoferrin Induces Apoptotic Cell Death With JNK/SAPK Activation in Oral Cancer Cells

et al. 2005

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Abstract. Lactoferrin, a member of the transferrin family, is iron-binding and a strongly cationic 76 kDa glycoprotein. In breast milk it is secreted in high concentrations from glandular epithelia and is also present in other exocrine fluids including saliva. In the present study, we examined the biological mechanisms of apoptosis induced by pepsin-digested-lactoferrin peptide (Lfn-p) in the human oral squamous cell carcinoma cell line SAS. We found that treatment with Lfn-p induced cell death with apoptotic nuclear changes, preceded by the cleavage of caspase-3 and poly (ADP-ribose) polymerase (PARP) in the apoptotic cells. Treatment with Lfn-p induced phosphorylation of extracellular signal-regulated kinase (ERK1 / 2), a member of the MAP kinase family, at early stages of apoptosis. Another MAP kinase, c-Jun N-terminal kinase / stressactivated protein kinase (JNK / SAPK), was also phosphorylated by treatment with Lfn-p. Pretreatment of SAS cells with SP600125, a JNK / SAPK inhibitor, diminished Lfn-induced apoptosis, as assessed by determining released lactate dehydrogenase activity. On the other hand, the MEK1 inhibitors PD98059 or U0126 showed no effect on repression of cell death, but rather an increase. These results suggest that JNK / SAPK activation may play an important role in Lfn-p-induced apoptotic cell death of human oral squamous cell carcinoma cells.

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“…[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%

“…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. 29) Moreover, bLF could inhibit tumor metastasis.…”

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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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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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Possible Chemopreventive Effects of Bovine Lactoferrin on Esophagus and Lung Carcinogenesis in the Rat

Cited by 76 publications

References 18 publications

Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma

Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma

Pepsin-Digested Bovine Lactoferrin Induces Apoptotic Cell Death With JNK/SAPK Activation in Oral Cancer Cells

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

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