Prevention of hepatocarcinogenesis with phosphatidylcholine and menaquinone-4: In vitro and in vivo experiments

Sakakima, Yoshikazu; Hayakawa, Akihiro; Nagasaka, Tetsuro; Nakao, Akimasa

doi:10.1016/j.jhep.2007.01.030

Cited by 48 publications

(39 citation statements)

References 29 publications

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“…(38) Here, we analyzed the inhibitory effect of lanreotide on the appearance of early hepatic preneoplastic events, using a twostage carcinogenic model combining DEN and AAF in rats. This model, and other similar models using carcinogens to induce preneoplastic changes, have already been used many times to assess chemoprevention (e.g., de Lujan Alvarez M et al, (30) Nakaji M et al, (39) and Sakakima Y et al (40) ). Athough not perfect, we believe the model allows a sequential analysis of the effect of chemoprevention after cell initiation, sometimes called the "first hit", by DEN injection; then the clonal expansion of these modified cells through promotion, leading to the formation of preneoplastic, reversible, foci.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of early preneoplastic events in the rat liver by the somatostatin analog lanreotide

et al. 2007

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Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death, and its incidence is increasing worldwide. Due to the known risk factors (mainly hepatitis B and C viruses), we believe there is a rationale for a chemopreventive approach to treat HCC. Here, based on described in vitro data, we evaluated the preventive effects of lanreotide, a somatostatin analog, on the induction of early carcinogenic events. We monitored preneoplastic foci induced by a two-stage initiation/promotion model of hepatocarcinogenesis in male Wistar rats, using diethylnitrosamine and 2-acetylaminofluorene. Lanreotide was given starting the day after the first diethylnitrosamine injection. By quantitative morphometry, we showed that lanreotide significantly decreases the size of induced preneoplastic foci. Analysis of proliferation and apoptosis assessed by immunohistochemistry, showed decreased proliferation and increased cell death in rats treated with lanreotide. As these events were associated with a significant decreased expression of the cell cycle regulator cyclin D1 and an increased expression of the cyclin-dependent kinase inhibitor p27 kip1 compared to the non-treated group, it is tempting to speculate that these factors are involved in the favorable effect of lanreotide. In conclusion, lanreotide significantly decreases early carcinogenic transformation in a two-step rat model. As lanreotide has a low toxicity profile, we believe it would be interesting to evaluate its effect in chemoprevention of HCC. (Cancer Sci 2007; 98: 1831-1839) H CC represents a major public health problem. Its incidence is in constant progression, with 2-5 new cases per 100 000 inhabitants/year in western countries and more than 20 per 100 000 inhabitants/year in Asia.(1,2) Curative treatment can only be proposed in 10-20% of cases.The main risk factors of HCC development are cirrhosis and hepatitis B and C that induce genetic alterations leading to preneoplastic, then neoplastic changes. The persistence of infection and/or cirrhosis often leads to tumoral relapse after surgical resection, observed in approximately 20% per year. Therefore, chemoprevention could play an important role in the therapeutic strategy of this disease.In experimental carcinogenesis, preneoplastic foci of altered hepatocytes emerge weeks or months before the appearance of hepatocellular adenomas and HCC.(3) Similar progression has been described in human hepatocarcinogenesis.(4) This fact has led to the development of a number of in vivo systems to study early neoplasia in rat liver.(5) The initiation-promotion or two-stage model of cancer development mimics the early events of the latent period of human carcinogenesis. The initiation stage of cancer development can be produced in rat liver by injection of DEN, (6) a carcinogen that causes DNA ethylation and mutagenesis.(7) Furthermore, DEN has been shown to induce tumors in rodents that closely mimic a subclass of human HCC. Somatostatin analogs (octreotide and lanreotide) are molecules that are widely...

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Section: Discussionmentioning

confidence: 99%

Inhibition of early preneoplastic events in the rat liver by the somatostatin analog lanreotide

et al. 2007

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“…Previous studies have revealed that VK2 are involved not only in Á-carboxylation of proteins but also in the Á-carboxylation independent function, thus suggesting that VK2 possess both Á-carboxylation-dependent and -independent actions (26). As an example of the Á-carboxylationindependent action of VK2, vitamin Ks has been demonstrated to have an anti-proliferative effect in many types of cancer cells including HCC (14,15,18,20,24,(26)(27)(28)(29)(30). In addition to anti-proliferative effects, VK2 also suppresses the invasion of HCC cells (18).…”

Section: Discussionmentioning

confidence: 99%

“…The administration of menatetrenone, a vitamin K2 (VK2) analogue, suppresses the recurrence of HCC after curative ablation therapy (16), or the development of HCC from cirrhotic livers (17) in the clinical setting. Vitamin K2 also suppresses the development and proliferation of HCC in vivo animal models (18)(19)(20). Otsuka et al showed that VK2 reduces the invasion of HCC cells as well as the proliferation of HCC cells in a protein kinase A (PKA)-dependent manner.…”

Section: Introductionmentioning

confidence: 99%

“…Otsuka et al showed that VK2 reduces the invasion of HCC cells as well as the proliferation of HCC cells in a protein kinase A (PKA)-dependent manner. Although the mechanisms involved in the growth suppression of HCC have been investigated and attributed to changes of cell cycle-related gene expression (18,20), the mechanisms by which VK2 inhibits the invasion of HCC are still not fully understood.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of matrix metalloproteinase expression by menatetrenone, a vitamin K2 analogue

Ide

Zhang²,

Hamajima³

et al. 2009

Oncol Rep

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Abstract. Vitamin K2 (VK2) has been shown to have a potent anti-tumor effect against several cancer types including hepatocellular carcinoma (HCC), but the mechanisms remain to be elucidated. Matrix metalloproteinase (MMP) plays an important role in the invasion and metastasis of cancer cells, but it is not known whether VK2 regulates the expression of MMPs. Human HCC cell lines were treated with VK2 combined with 12-O-tetradecanoyl phorbol-13 acetate (TPA) and the expression of MMPs was examined by reporter gene assay, RT-PCR and Western blotting. VK2 inhibited the basal and TPA-induced expression of MMP-1, -3 and -7 at the transcriptional, mRNA and protein levels in a dosedependent manner. VK2 also inhibited the TPA-induced activation of NF-κB and AP-1 activity. The inhibitors against NF-κB and mitogen-activated protein kinases (MAP kinase) including ERK and JNK pathways suppressed TPA-induced luciferase activity of MMP-1, -3 and -7 promoters. These data suggest that VK2 inhibits MMP expression by suppressing NF-κB and MAP kinase activity and might be potentially useful in the treatment of HCC.

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“…They not only determine the flow of minerals, nutrients and drugs into the cell but also influence the communication between brain cells directing the shape of receptors and promoting the growth of dendrites. Several studies have been made to show beneficial effects of PLs in tumor and metastasis inhibition 2,3 .…”

Section: Introductionmentioning

confidence: 99%

Studies on Preparation of Lysophospholipids from Soybean Phospholipids Using Lipozyme TL IM Immobilized Enzyme

2017

Chem Sci Trans

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Soybean lysophospholipids (SBLPLs), produced from soybean phospholipids (SBPLs), are important cell signaling and growth factor molecules related to different cardiovascular functions. SBLPLs help to prevent different diseases like cancer and neurological disorders. It has considerable role in membrane chemistry and biochemistry and also in many physiological and pathological processes. In this investigation, SBLPLs were prepared from crude SBPLs which are a byproduct of soybean oil refinery industry. The methods adopted include deoiling of crude SBPLs and treating with butanol in hexane medium using 1, 3-specific Lipozyme TL IM immobilized lipase from Thermomyces lanuginosus at 40 o C. The final product contains significant amount of LPLs alongwith other phospholipids.

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Prevention of hepatocarcinogenesis with phosphatidylcholine and menaquinone-4: In vitro and in vivo experiments

Cited by 48 publications

References 29 publications

Inhibition of early preneoplastic events in the rat liver by the somatostatin analog lanreotide

Inhibition of early preneoplastic events in the rat liver by the somatostatin analog lanreotide

Inhibition of matrix metalloproteinase expression by menatetrenone, a vitamin K2 analogue

Studies on Preparation of Lysophospholipids from Soybean Phospholipids Using Lipozyme TL IM Immobilized Enzyme

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