Antitumor and Cancer-preventative Function of Fucoxanthin: A Marine Carotenoid.

Fucoxanthin is a marine carotenoid mainly found in brown seaweeds. Its antitumor and cancer-preventative function has been extensively investigated. Investigations have indicated that fucoxanthin and its metabolite fucoxanthinol induce G cell-cycle arrest and apoptosis in various cell lines and can inhibit cancer development in animal models.

Inhibition of the enzyme activity of cytochrome P450 1A1, 1A2 and 3A4 by fucoxanthin, a marine carotenoid.

Fucoxanthin is a carotenoid that is mainly identified in brown algae and is known to have anticarcinogenic and anti-tumor activities. Carotenoids have generally been shown to induce the expression and enzyme activity of the cytochrome P450s (CYPs). The present study evaluated the effect of fucoxanthin on the expression and enzymatic activity of the major xenobiotic metabolizing enzymes, CYP1A1, CYP1A2 and CYP3A4.

Chronic inflammation-derived nitric oxide causes conversion of human colonic adenoma cells into adenocarcinoma cells.

It has been suggested that nitric oxide (NO) derived from chronically inflamed tissues is a cause of carcinogenesis. We herein demonstrated that administration of an inducible NO synthase inhibitor, aminoguanidine, significantly suppressed the tumorigenic conversion of human colonic adenoma (FPCK-1-1) cells into adenocarcinoma (FPCK/Inflam) cells accelerated by foreign body-induced chronic inflammation in nude mice. To determine whether NO directly promotes carcinogenesis, we exposed FPCK-1-1 cells continuously to chemically generated NO (FPCK/NO), and periodically examined their tumorigenicity.

Fucoxanthin induces GADD45A expression and G1 arrest with SAPK/JNK activation in LNCap human prostate cancer cells.

Background/aim: The antitumor effect of fucoxanthin, a marine carotenoid found in brown algae, was investigated on prostate cancer cells.

Materials And Methods: LNCap prostate cancer cells were treated with fucoxanthin and the effects were evaluated in relation to cell proliferation, cell cycle, expression of growth arrest, DNA damage-inducible protein (GADD45) genes, and phosphorylation status of mitogen-activated protein kinases.

Results: Fucoxanthin inhibited the growth of LNCap prostate cancer cells in a dose-dependent manner.

Implication of mitogen-activated protein kinase in the induction of G1 cell cycle arrest and gadd45 expression by the carotenoid fucoxanthin in human cancer cells.

Background: The precise mechanism of the anti-tumor action of fucoxanthin has yet to be elucidated. We previously reported that gadd45a and gadd45b might play a role in the G1 arrest induced by fucoxanthin. In the present study, we show that several MAPKs modulate the induction of gadd45 and G1 arrest

Methods: HepG2 and DU145 cells were used.

Cancer prevention by carotenoids.

Various natural carotenoids seem to be valuable for cancer prevention, and these carotenoids may be more suitable in combinational use, rather than in single use. In fact, we have proven that combinational use of natural carotenoids resulted in significant suppression of liver cancer. Patients of viral hepatitis with cirrhosis were administered with beta-cryptoxanthin-enriched Mandarin orange juice, in addition to capsules of carotenoids mixture.

Combination analysis of three polymorphisms for predicting the risk for steroid-induced osteonecrosis of the femoral head.

Background: Osteonecrosis of the femoral head (ONF) often develops following corticosteroid administration. We previously investigated the genetic background for the development of corticosteroid-induced ONF and found relations between ONF development and genetic polymorphisms in the ATP binding cassette B1 (ABCB1) gene (C3435T), apolipoprotein B (ApoB) gene (C7623T), and cAMP-response element binding protein-binding protein (CBP) gene (rs3751845). In the present study, we examined whether combined information regarding these three single nucleotide polymorphisms (SNPs) in the ABCB1, ApoB, and CBP genes is useful for predicting ONF development.

Production of the monoterpene limonene and modulation of apoptosis-related proteins in embryonic-mouse NIH 3T3 fibroblast cells by introduction of the limonene synthase gene isolated from Japanese catnip (Schizonepeta tenuifolia).

The monoterpene D-limonene shows cancer preventative and cancer therapeutic activities in vitro and in vivo. Unlike plants, animals are unable to synthesize limonene de novo and obtain limonene through dietary sources. In the present study we established transgenic mouse embryonic NIH 3T3 fibroblast cells that produce limonene by introducing the D-limonene synthase gene obtained from Japanese catnip (Schizonepeta tenuifolia).

Cancer control by phytochemicals.

Chemoprevention is one of the most important strategy in the field of cancer control. Molecular mechanism-based cancer chemoprevention by phytochemicals seems to be very attractive method. In this review, possible molecular targets for cancer prevention are overviewed, and some examples of cancer preventive phytochemicals, such as carotenoids, are presented.

Halocynthiaxanthin and peridinin sensitize colon cancer cell lines to tumor necrosis factor-related apoptosis-inducing ligand.

Carotenoids are compounds contained in foods and possess anticarcinogenic activity. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer therapeutics due to its ability to induce apoptosis selectively in cancer cells. However, some tumors remain tolerant to TRAIL-induced apoptosis.

ApoB C7623T polymorphism predicts risk for steroid-induced osteonecrosis of the femoral head after renal transplantation.

Background: Nontraumatic osteonecrosis of the femoral head (ONFH) is caused by disruption of blood flow. This disease often occurs in association with steroid treatment. The pathology of steroid-induced ONFH remains unclear, although abnormalities in lipid metabolism have been reported to be involved.

Fucoxanthin, a natural carotenoid, induces G1 arrest and GADD45 gene expression in human cancer cells.

Background: Although the antitumor effects of fucoxanthin are known, the precise mechanism of action has yet to be elucidated.

Materials And Methods: HepG2 and DU145 cells were used for these investigations. The effect of fucoxanthin on gene expression was assayed using a DNA microarray system.

Low molecular weight phenotype of Apo(a) is a risk factor of corticosteroid-induced osteonecrosis of the femoral head after renal transplant.

Objective: Osteonecrosis of the femoral head (ONF) is a necrosis due to disruption of the blood flow. The disease often occurs in association with corticosteroid treatment. The pathology of corticosteroid-induced ONF is unclear, although abnormalities in the coagulation and fibrinolytic systems or in the lipid metabolism have been reported to be involved.

Glycyrrhetinic acid and related compounds induce G1 arrest and apoptosis in human hepatocellular carcinoma HepG2.

Glycyrrhetinic acid (GA) and its related compounds are known to have anti-inflammatory activity and also to inhibit liver carcinogenesis and tumor growth. GA and related compounds inhibited cell proliferation of the human hepatoma cell line, HepG2. Among five compounds tested, ursolic acid and 18beta-olean-12-ene-3beta, 23, 28-triol (18beta-erythrotriol) were comparatively effective, where the 50% inhibitory dose was 20 microM and 25 microM, respectively.

Cancer prevention by phytochemicals.

Information has been accumulated indicating that diets rich in vegetables and fruits can reduce the risk of a number of chronic diseases, including cancer, cardiovascular disease, diabetes and age-related macular degeneration. Phytochemicals (various factors in plant foods), such as carotenoids, antioxidative vitamins, phenolic compounds, terpenoids, steroids, indoles and fibers, have been considered responsible for the risk reduction. Among them, a mixture of natural carotenoids has been studied extensively and proven to show beneficial effects on human cancer prevention.

Tumor suppressive effects of tocotrienol in vivo and in vitro.

Tocotrienols have been reported to have higher biological activities than tocopherols. We investigated the antitumor effect of tocotrienols both in vivo and in vitro. Oral administration of tocotrienols resulted in significant suppression of liver and lung carcinogenesis in mice.

Cancer prevention by antioxidants.

Various antioxidants in foods, such as phenolic compounds and carotenoids, were proven to have anticarcinogenic activity. In the case of carotenoids, the mixture of them was found to be very effective. In fact, the development of hepatoma in the high risk group of liver cancer, was significantly suppressed by the treatment with natural carotenoids mixture.

Genistein induces Gadd45 gene and G2/M cell cycle arrest in the DU145 human prostate cancer cell line.

Genistein is the most abundant isoflavone of soybeans and has been shown to cause growth arrest in various human cancer cell lines. However, the precise mechanism for this is still unclear. We report here that the growth arrest and DNA damage-inducible gene 45 (gadd45) gene is induced by genistein via its promoter in a DU145 human prostate cancer cell line.

Effects of ethanol on the induction of uncoupling protein-1 (UCP1) mRNA in the mouse brown adipose tissue.

Expression of uncoupling protein-1 (UCP1) is increased by cold acclimation and overfeeding, and reduced in fasting and genetic obesity. It is known that the mitochondrial UCP1 in the brown adipose tissue (BAT) is an important key molecule for non-shivering thermogenesis. On the other hand, ethanol (EtOH) alters thermoregulation in humans and laboratory animals.

Production of phytoene, a carotenoid, and induction of connexin 26 in transgenic mice carrying the phytoene synthase gene crtB.

Carotenoids have been recognized as chemopreventive agents against human diseases, such as cancer and cardiovascular disease. Mammalians utilize carotenoids supplied from their food since they are unable to perform the de novo synthesis of carotenoids. We previously created mammalian cultured cells producing phytoene, a type of carotenoid, and showed that these cells acquired resistance against oxidative stress and oncogenic transformation.

Induction of cell cycle arrest and p21(CIP1/WAF1) expression in human lung cancer cells by isoliquiritigenin.

Isoliquiritigenin is a natural flavonoid isolated from licorice, shallot and bean sprouts. The effect of isoliquiritigenin on cell proliferation and cell cycle progression was examined in the A549 human lung cancer cell line. Isoliquiritigenin significantly inhibited the proliferation of lung cancer cells in a dose- and time-dependent manner.

Relationship between postrenal transplant osteonecrosis of the femoral head and gene polymorphisms related to the coagulation and fibrinolytic systems in Japanese subjects.

Background: Nontraumatic osteonecrosis of the femoral head (ONFH) is one of the complications that may occur after renal transplantation. We investigated the relationship between the incidence of ONFH and polymorphisms in the genes for plasminogen activator inhibitor (PAI)-1, which is one of the major regulatory proteins of the fibrinolytic system, and 5,10-methylenetetrahydrofolate reductase (MTHFR), which is associated with the plasma levels of homocysteine in Japanese subjects.

Methods: Thirty-one patients with postrenal transplant ONFH and 106 patients without ONFH were selected.

H-ras mutations at codon 61 or 13 in tumors initiated with a NO donor in mouse skin.

The tumor-initiating activity of nitric oxide (NO) in carcinogenesis was assessed using (+/-)-(E)-4-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexenamide (NOR1), a synthetic NO donor. Topical application of NOR1 followed by 12-O-tetradecanoylphorbol 13-acetate (TPA) treatment twice a week for 20 weeks resulted in the development of papillomas in mice. All of the papillomas examined contained H-ras mutations at codons 61 or 13.

Genetic analysis of steroid-induced osteonecrosis of the femoral head.

With advanced organ transplantation technology, steroid-induced osteonecrosis of the femoral head (ONF) is one of the most troublesome complications. Steroid sensitivity varies among individuals, and the involvement of polymorphism of various genes relating to steroid metabolism is suggested. The present study investigated the relation between single nucleotide polymorphism (SNP) on the DNA sequence of cytochrome p(450) and ONF development.

Cancer Chemoprevention by Phytochemicals and their Related Compounds.

Cancer chemoprevention by phytochemicals may be one of the most feasible approaches for cancer control. For example, phytochemicals obtained from vegetables, fruits, spices, teas, herbs and medicinal plants, such as carotenoids, phenolic compounds and terpenoids, have been proven to suppress experimental carcinogenesis in various organs. These candidates should be evaluated by intervention studies, before acceptance as cancer preventive agents for human application.