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Sensitization by dietary docosahexaenoic acid of rat mammary carcinoma to anthracycline: a role for tumor vascularization.
Colas S, Maheo K, Denis F, Goupille C, Hoinard C, Champeroux P, Tranquart F, Bougnoux P.
Institut National de la Sante et de la Recherche Medicale, E0211 Nutrition Croissance et Cancer, CHU Bretonneau, 2 bis Boulevard Tonnelle, F-37044 Tours, France.
PURPOSE: To investigate whether dietary docosahexaenoic acid (DHA), a peroxidizable polyunsaturated omega-3 fatty acids, sensitizes rat mammary tumors to anthracyclines and whether its action interferes with tumor vascularization, a critical determinant of tumor growth. EXPERIMENTAL DESIGN: Female Sprague-Dawley rats were initiated by N-methylnitrosourea to develop mammary tumors and then assigned to a control group (n = 18), receiving a supplementation of palm oil, or to a DHA group (n = 54), supplemented with a microalgae-produced oil (DHASCO, 1.5 g/d). The DHA group was equally subdivided into three subgroups with addition of different amounts of alpha-tocopherol. Epirubicin was injected weekly during 6 weeks after the largest tumor reached 1.5 cm(2), and subsequent changes in the tumor surface were evaluated. Tumor vascularization was assessed by power Doppler sonography before and during chemotherapy. RESULTS: DHA and alpha-tocopherol were readily absorbed and incorporated into rat tissues. Epirubicin induced a 45% mammary tumor regression in the DHA-supplemented group, whereas no tumor regression was observed in the control group. In the DHA group, before chemotherapy was initiated, tumor vascular density was 43% lower than in the control group and remained lower during chemotherapy. Enhancement of epirubicin efficacy by DHA was abolished in a dose-dependent manner by alpha-tocopherol, and the same trend was observed for DHA-induced reduction in tumor vascular density. CONCLUSIONS: Dietary DHA supplementation led to a reduction in tumor vascularization before the enhancement of any response to anthracyclines, suggesting that DHA chemosensitizes mammary tumors through an inhibition of the host vascular response to the tumor.
PMID: 17020996 [PubMed - indexed for MEDLINE]
Red palm oil suppresses the formation of azoxymethane (AOM) induced aberrant crypt foci (ACF) in Fisher 344 male rats.
Boateng J, Verghese M, Chawan CB, Shackelford L, Walker LT, Khatiwada J, Williams DS.
Nutrition Biochemistry and Carcinogenesis Laboratory, Department of Food and Animal Sciences, Alabama A&M University, P.O. Box 1628, Normal, 35762, USA.
Red palm oil (RPO) contains significant levels of carotenoids and Vitamin E. In this experiment we compared the inhibitory effects of RPO (7% and 14% levels) and soybean oil (7% and 14%) on azoxymethane (AOM) induced aberrant crypt foci (ACF). Thirty-two male Fisher 344 rats were randomly assigned to four groups. Two groups received AIN-93 G control (C) diet containing 7% and 14% soybean oil (SBO), respectively. Groups 3 and 4 received a treatment diet consisting of 7% and 14% RPO, respectively. The rats received subcutaneous injections of AOM at 16 mg/kg body weight at 7 and 8 weeks of age. At 17 weeks of age rats were killed by CO(2) asphyxiation. Numbers of ACF (mean+/-SE) in the proximal and distal colon were: 39.9 +/- 0.9, 53.8 +/- 2.8, 26.0 +/- 3.0, 27.5 +/- 1.5 and 118.2 +/- 1.7, 125.6 +/- 3.2, 41 +/- 7, 52.3 +/- 1.8 in rats fed 7% SBO, 14% SBO, 7% RPO and 14% RPO, respectively. The results of this study showed that RPO reduced the incidence of AOM induced ACF and may therefore have a beneficial effect in reducing the incidence of colon cancer.
PMID: 16822603 [PubMed - indexed for MEDLINE]
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Tocotrienol-rich fraction of palm oil induces cell cycle arrest and apoptosis selectively in human prostate cancer cells.
Srivastava JK, Gupta S.
Department of Urology, Case Western Reserve University, Cleveland, OH 44106, USA.
One of the requisite of cancer chemopreventive agent is elimination of damaged or malignant cells through cell cycle inhibition or induction of apoptosis without affecting normal cells. In this study, employing normal human prostate epithelial cells (PrEC), virally transformed normal human prostate epithelial cells (PZ-HPV-7), and human prostate cancer cells (LNCaP, DU145, and PC-3), we evaluated the growth-inhibitory and apoptotic effects of tocotrienol-rich fraction (TRF) extracted from palm oil. TRF treatment to PrEC and PZ-HPV-7 resulted in almost identical growth-inhibitory responses of low magnitude. In sharp contrast, TRF treatment resulted in significant decreases in cell viability and colony formation in all three prostate cancer cell lines. The IC(50) values after 24h TRF treatment in LNCaP, PC-3, and DU145 cells were in the order 16.5, 17.5, and 22.0 microg/ml. TRF treatment resulted in significant apoptosis in all the cell lines as evident from (i) DNA fragmentation, (ii) fluorescence microscopy, and (iii) cell death detection ELISA, whereas the PrEC and PZ-HPV-7 cells did not undergo apoptosis, but showed modestly decreased cell viability only at a high dose of 80 microg/ml. In cell cycle analysis, TRF (10-40 microg/ml) resulted in a dose-dependent G0/G1 phase arrest and sub G1 accumulation in all three cancer cell lines but not in PZ-HPV-7 cells. These results suggest that the palm oil derivative TRF is capable of selectively inhibiting cellular proliferation and accelerating apoptotic events in prostate cancer cells. TRF offers significant promise as a chemopreventive and/or therapeutic agent against prostate cancer.
PMID: 16762318 [PubMed - indexed for MEDLINE]
Tocotrienol-rich fraction from palm oil and gene expression in human breast cancer cells.
Nesaretnam K, Ambra R, Selvaduray KR, Radhakrishnan A, Canali R, Virgili F.
Malaysian Palm Oil Board, 6 Persiaran Institusi, Bandar Baru Bangi, 4300 Kajang, Selangor, Malaysia. sarnesar@mpob.gov.my
Vitamin E is important not only for its cellular antioxidant and lipid-lowering properties, but also as an antiproliferating agent. It has also been shown to contribute to immunoregulation, antibody production, and resistance to implanted tumors. It has recently been shown that tocotrienols are the components of vitamin E responsible for growth inhibition in human breast cancer cells in vitro as well as in vivo through estrogen-independent mechanisms. Although tocotrienols act on cell proliferation in a dose-dependent manner and can induce programmed cell death, no specific gene regulation has yet been identified. In order to investigate the molecular basis of the effect of a tocotrienol-rich fraction (TRF) from palm oil, we performed a cDNA array analysis of cancer-related gene expression in estrogen-dependent (MCF-7) and estrogen-independent (MDA-MB-231) human breast cancer cells. The human breast cancer cells were incubated with or without 8 mug/mL of tocotrienols for 72 h. RNA was subsequently extracted and subjected to reverse transcription before being hybridized onto cancer arrays. Tocotrienol supplementation modulated significantly 46 out of 1200 genes in MDA-MB-231 cells. In MCF-7 cells, tocotrienol administration was associated with a lower number of affected genes. Interestingly, only three were affected in a similar fashion in both cell lines: c-myc binding protein MM-1, 23-kDa highly basic protein, and interferon-inducible protein 9-27 (IFITM-1). These proteins are most likely involved in the cell cycle and can exert inhibitory effects on cell growth and differentiation of the tumor cell lines. These data suggest that tocotrienols are able to affect cell homeostasis, possibly independent of their antioxidant activity.
PMID: 15753141 [PubMed - indexed for MEDLINE]
Tocotrienol-rich fraction from palm oil affects gene expression in tumors resulting from MCF-7 cell inoculation in athymic mice.
Nesaretnam K, Ambra R, Selvaduray KR, Radhakrishnan A, Reimann K, Razak G, Virgili F.
Malaysian Palm Oil Board, Bandar Baru Bangi, 4300 Selangor, Malaysia. sarnesar@mpob.gov.my
It has recently been shown that tocotrienols are the components of vitamin E responsible for inhibiting the growth of human breast cancer cells in vitro, through an estrogen-independent mechanism. Although tocotrienols act on cell proliferation in a dose-dependent manner and can induce programmed cell death, no specific gene regulation has yet been identified. To investigate the molecular basis of the effect of tocotrienols, we injected MCF-7 breast cancer cells into athymic nude mice. Mice were fed orally with 1 mg/d of tocotrienol-rich fraction (TRF) for 20 wk. At end of the 20 wk, there was a significant delay in the onset, incidence, and size of the tumors in nude mice supplemented with TRF compared with the controls. At autopsy, the tumor tissue was excised and analyzed for gene expression by means of a cDNA array technique. Thirty out of 1176 genes were significantly affected. Ten genes were downregulated and 20 genes up-regulated with respect to untreated animals, and some genes in particular were involved in regulating the immune system and its function. The expression of the interferon-inducible transmembrane protein-1 gene was significantly up-regulated in tumors excised from TRF-treated animals compared with control mice. Within the group of genes related to the immune system, we also found that the CD59 glycoprotein precursor gene was up-regulated. Among the functional class of intracellular transducers/effectors/modulators, the c-myc gene was significantly down-regulated in tumors by TRF treatment. Our observations indicate that TRF supplementation significantly and specifically affects MCF-7 cell response after tumor formation in vivo and therefore the host immune function. The observed effect on gene expression is possibly exerted independently from the antioxidant activity typical of this family of molecules.
PMID: 15506241 [PubMed - indexed for MEDLINE]
Enhanced radiosensitivity of rat autochthonous mammary tumors by dietary docosahexaenoic acid.
Colas S, Paon L, Denis F, Prat M, Louisot P, Hoinard C, Le Floch O, Ogilvie G, Bougnoux P.
Nutrition Croissance et Cancer, INSERM E 0211, IFR 120, CHU Bretonneau, Tours, France.
Dietary docosahexaenoic acid (DHA), which integrates into tumor cell membranes, has been reported to enhance the efficacy against tumors of cytotoxic drugs that induce reactive oxygen species (ROS). Because ionizing radiation also generate ROS, we initiated a study to determine whether dietary DHA might sensitize mammary tumors to irradiation. Mammary tumors were induced by N-methylnitrosourea (NMU) in Sprague-Dawley rats. The optimal dose of radiation to examine the effect of DHA on tumor response to irradiation was determined to be 18 grays (Gy) using a 4-6 MeV electron beam (according to the depth of the target volume) delivered in a single fraction from a linear accelerator. Two groups of rats were fed a basal diet containing 7% of a mixture of peanut and rapeseed oils enriched with 8% of an oil containing either a low (palm oil) or high (DHASCO oil containing 40% DHA) DHA content. DHA group was equally subdivided into 2 groups without or with addition of vitamin E (100 IU/kg diet). Irradiation was carried out when the first tumor in each rat reached 1.5 cm2 and subsequent change in tumor size was documented over time. DHA level in adipose tissue, taken as a biomarker, was higher in the DHA supplemented group compared to the control group. Vitamin E level in liver, the best storage for this compound, was higher in the vitamin E supplemented DHA group compared to the DHA group. Tumor size decreased by 60% at 12 days after irradiation in the DHA group vs. 31% in the control group (p = 0.03) and 36% in the DHA plus vitamin E group. Therefore, dietary DHA sensitized mammary tumors to radiation. The addition of vitamin E inhibited the beneficial effect of DHA, suggesting that this effect might be mediated by oxidative damage to the peroxidizable lipids. Copyright 2004 Wiley-Liss, Inc.
PMID: 14961586 [PubMed - indexed for MEDLINE]
Tocotrienol-rich fraction of palm oil activates p53, modulates Bax/Bcl2 ratio and induces apoptosis independent of cell cycle association.
Agarwal MK, Agarwal ML, Athar M, Gupta S.
Department of Medical Elementology and Toxicology, Hamdard University, New Delhi, India.
Anti-cancer properties of palm oil have been attributed to the presence of tocotrienols and carotenoids. Studies from various laboratories have shown that tocotrienol-rich fraction (TRF) of palm oil inhibits cell growth and induces apoptosis in both preneoplastic and neoplastic cells. However, the mechanism by which TRF induces apoptosis remains largely unknown. Since several chemopreventive agents have been shown to utilize p53 pathway in negative regulation of cell growth, using human colon carcinoma RKO cells which express wild type p53, we investigated the effect of TRF on components of p53 signaling network. Treatment of cells with TRF resulted in a dose- and time- dependent inhibition of growth and colony formation. Further, TRF treatment of RKO cells resulted in the induction of WAF1/p21 which appears to be independent of cell cycle regulation and is transcriptionally upregulated in p53 dependent fashion. These results were further confirmed by using cells that express luciferase from a p53 responsive promoter where TRF treatment leads to activation of p53 reporter activity. TRF treatment also resulted in alteration in Bax/Bcl2 ratio in favor of apoptosis, which was associated with the release of cytochrome c and induction of apoptotic protease-activating factor-1. This altered expression of Bcl2 family members triggered the activation of initiator caspase-9 followed by activation of effector caspase-3. These signaling cascades lead to condensed chromatin, DNA fragmentation and shrinkage of cell membrane resulting into apoptosis. Our data suggest that TRF-induced apoptosis in colon carcinoma cells is mediated by p53 signaling network which appears to be independent of cell cycle association.
PMID: 14712090 [PubMed - indexed for MEDLINE]
Phytonutrient deficiency: the place of palm fruit.
Wattanapenpaiboon N, Wahlqvist MW.
Asia Pacific Health and Nutrition Centre, Monash Asia Institute, 8th Floor Menzies Building, Monash University,Wellington Road, Clayton, Melbourne, Victoria 3800, Australia. tikky.w@adm.monash.edu.au
The oil palm (Elaeis guineensis) is native to many West African countries, where local populations have used its oil for culinary and other purposes. Large-scale plantations, established principally in tropical regions (Asia, Africa and Latin America), are mostly aimed at the production of oil, which is extracted from the fleshy mesocarp of the palm fruit, and endosperm or kernel oil. Palm oil is different from other plant and animal oils in that it contains 50% saturated fatty acids, 40% unsaturated fatty acids, and 10% polyunsaturated fatty acids. The fruit also contains components that can endow the oil with nutritional and health beneficial properties. These phytonutrients include carotenoids (alpha-,beta-,and gamma-carotenes), vitamin E (tocopherols and tocotrienols), sterols (sitosterol, stigmasterol and campesterol), phospholipids, glycolipids and squalene. In addition, it is recently reported that certain water-soluble powerful antioxidants, phenolic acids and flavonoids, can be recovered from palm oil mill effluent. Owing to its high content of phytonutrients with antioxidant properties, the possibility exists that palm fruit offers some health advantages by reducing lipid oxidation, oxidative stress and free radical damage. Accordingly, use of palm fruit or its phytonutrient-rich fractions, particularly water-soluble antioxidants, may confer some protection against a number of disorders or diseases including cardiovascular disease, cancers, cataracts and macular degeneration, cognitive impairment and Alzheimer's disease. However, whilst prevention of disease through use of these phytonutrients as in either food ingredients or nutraceuticals may be a worthwhile objective, dose response data are required to evaluate their pharmacologic and toxicologic effects. In addition, one area of concern about use of antioxidant phytonutrients is how much suppression of oxidation may be compatible with good health, as toxic free radicals are required for defence mechanisms. These food-health concepts would probably spur the large-scale oil palm (and monoculture) plantations, which are already seen to be a major cause of deforestation and replacement of diverse ecosystems in many countries. However, the environmental advantages of palm phytonutrients are that they are prepared from the readily available raw material from palm oil milling processes. Palm fruit, one of only a few fatty fruits, is likely to have an increasingly substantiated place in human health, not only through the provision of acceptable dietary fats, but also its characteristic protective phytonutrients.
Publication Types:
PMID: 14506002 [PubMed - indexed for MEDLINE]
Palm fruit chemistry and nutrition.
Sundram K, Sambanthamurthi R, Tan YA.
Malaysian Palm Oil Board, P.O. Box 10620, 50720 Kuala Lumpur, Malaysia. kalyana@mpob.gov.my
The palm fruit (Elaies guineensis) yields palm oil, a palmitic-oleic rich semi solid fat and the fat-soluble minor components, vitamin E (tocopherols, tocotrienols), carotenoids and phytosterols. A recent innovation has led to the recovery and concentration of water-soluble antioxidants from palm oil milling waste, characterized by its high content of phenolic acids and flavonoids. These natural ingredients pose both challenges and opportunities for the food and nutraceutical industries. Palm oil's rich content of saturated and monounsaturated fatty acids has actually been turned into an asset in view of current dietary recommendations aimed at zero trans content in solid fats such as margarine, shortenings and frying fats. Using palm oil in combination with other oils and fats facilitates the development of a new generation of fat products that can be tailored to meet most current dietary recommendations. The wide range of natural palm oil fractions, differing in their physico-chemical characteristics, the most notable of which is the carotenoid-rich red palm oil further assists this. Palm vitamin E (30% tocopherols, 70% tocotrienols) has been extensively researched for its nutritional and health properties, including antioxidant activities, cholesterol lowering, anti-cancer effects and protection against atherosclerosis. These are attributed largely to its tocotrienol content. A relatively new output from the oil palm fruit is the water-soluble phenolic-flavonoid-rich antioxidant complex. This has potent antioxidant properties coupled with beneficial effects against skin, breast and other cancers. Enabled by its water solubility, this is currently being tested for use as nutraceuticals and in cosmetics with potential benefits against skin aging. A further challenge would be to package all these palm ingredients into a single functional food for better nutrition and health.
Publication Types:
PMID: 14506001 [PubMed - indexed for MEDLINE]
Role of caspase-8 activation in mediating vitamin E-induced apoptosis in murine mammary cancer cells.
Shah S, Gapor A, Sylvester PW.
College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209-0470, USA.
The vitamin E family of compounds is divided into two subgroups, tocopherols and tocotrienols. However, tocotrienols display more potent apoptotic activity in mammary cancer cells. Although the mechanism(s) mediating tocotrienol-induced apoptosis is presently unknown, apoptosis is carried out by activation of initiator caspases (caspase-8 or -9) that subsequently activate effector caspases (caspase-3, -6, or -7). Studies were conducted to determine whether tocotrienol-induced apoptosis is mediated by activation of the caspase-8 and/or caspase-9 pathway. Highly malignant +SA mouse mammary epithelial cells were grown in culture and maintained on serum-free media. Treatment with tocotrienol-rich-fraction of palm oil (TRF) and g-tocotrienol, but not a-tocopherol, induced a dose-dependent decrease in +SA cell viability. TRF- and g-tocotrienol-induced cell death resulted from apoptosis, as determined by DNA fragmentation and positive TUNEL assay staining. Additional studies showed that treatment with 50 mM TRF or 20 mM g-tocotrienol increased intracellular activity and levels of processed caspase-8 and -3 but not caspase-9. Furthermore, treatment with specific caspase-8 or -3 inhibitors, but not caspase-9 inhibitor, completely blocked the tocotrienol-induced apoptosis in +SA cells. These findings demonstrate that tocotrienol-induced apoptosis in +SA mammary cancer cells is mediated through activation of the caspase-8 signaling pathway and is independent of caspase-9 activation.
PMID: 12881019 [PubMed - indexed for MEDLINE]
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Palm oil alleviates 12-O-tetradecanoyl-phorbol-13-acetate-induced tumor promotion response in murine skin.
Kausar H, Bhasin G, Zargar MA, Athar M.
Department of Medical Elementology and Toxicology, Faculty of Science, Hamdard University, 110062, New Delhi, India.
Palm oil is a rich source of vitamin E, carotenoids, tocotrienols and tocopherols which are natural antioxidants and act as scavengers of oxygen free radicals. 12-O-Tetradecanoyl-phorbol-13-acetate (TPA) is a known oxidant that promotes tumorigenesis in mouse skin through the elaboration of oxidative stress. In this study we therefore assessed the anti-tumor promoting potential of palm oil against TPA-mediated skin tumorigenesis in 7,12-dimethylbenz[a]anthracene-initiated Swiss albino mice. Topical application of palm oil 1 h prior to application of TPA resulted in a significant protection against skin tumor promotion. The animals pre-treated with palm oil showed a decrease in both tumor incidence and tumor yield as compared to the TPA (alone)-treated group. Palm oil application also reduced the development of malignant tumors. Since TPA-induced epidermal ornithine decarboxylase (ODC) activity and [(3)H]thymidine incorporation are conventionally used markers of skin tumor promotion, we also assessed the effect of pre-application of palm oil on these parameters, and it was observed that the application of palm oil prior to the application of TPA alleviated both these TPA-induced markers of tumor promotion. The effect of pre-application of palm oil on TPA-mediated depletion in the non-enzymatic and enzymatic molecules was also assessed and it was observed that palm oil application prior to TPA application resulted in the recovery of TPA-mediated depletion in the levels of these molecules viz. glutathione, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and catalase. Similarly, palm oil also exhibited a protective effect against Fe(2+)-ascorbate-induced lipid peroxidation in the epidermal microsomes. The results of the present study thus suggest that palm oil possesses anti-skin tumor promoting effects, and that the mechanism of such effects may involve the inhibition of tumor promoter-induced epidermal ODC activity, [(3)H]thymidine incorporation and cutaneous oxidative stress.
PMID: 12668279 [PubMed - indexed for MEDLINE]
Palm oil: biochemical, physiological, nutritional, hematological, and toxicological aspects: a review.
Edem DO.
Department of Chemistry and Biochemistry, University of Uyo, Uyo, Akwa Ibom State, Nigeria.
The link between dietary fats and cardiovascular diseases has necessitated a growing research interest in palm oil, the second largest consumed vegetable oil in the world. Palm oil, obtained from a tropical plant, Elaeis guineensis contains 50% saturated fatty acids, yet it does not promote atherosclerosis and arterial thrombosis. The saturated fatty acid to unsaturated fatty acid ratio of palm oil is close to unity and it contains a high amount of the antioxidants, beta-carotene, and vitamin E. Although palm oil-based diets induce a higher blood cholesterol level than do corn, soybean, safflower seed, and sunflower oils, the consumption of palm oil causes the endogenous cholesterol level to drop. This phenomenon seems to arise from the presence of the tocotrienols and the peculiar isomeric position of its fatty acids. The benefits of palm oil to health include reduction in risk of arterial thrombosis and atherosclerosis, inhibition of endogenous cholesterol biosynthesis, platelet aggregation, and reduction in blood pressure. Palm oil has been used in the fresh state and/or at various levels of oxidation. Oxidation is a result of processing the oil for various culinary purposes. However, a considerable amount of the commonly used palm oil is in the oxidized state, which poses potential dangers to the biochemical and physiological functions of the body. Unlike fresh palm oil, oxidized palm oil induces an adverse lipid profile, reproductive toxicity and toxicity of the kidney, lung, liver, and heart. This may be as a result of the generation of toxicants brought on by oxidation. In contrast to oxidized palm oil, red or refined palm oil at moderate levels in the diet of experimental animals promotes efficient utilization of nutrients, favorable body weight gains, induction of hepatic drug metabolizing enzymes, adequate hemoglobinization of red cells and improvement of immune function. Howerer, high palm oil levels in the diet induce toxicity to the liver as shown by loss of cellular radial architecture and cell size reductions which are corroborated by alanine transaminase to asparate transaminase ratios which are higher than unity. The consumtion of moderate amounts of palm oil and reduction in the level of oxidation may reduce the health risk believed to be associated with the consumption of palm oil. Red palm oil, by virtue of its beta-carotene content, may protect against vitamin A deficiency and certain forms of cancer.
Publication Types:
PMID: 12602939 [PubMed - indexed for MEDLINE]
Role of GTP-binding proteins in reversing the antiproliferative effects of tocotrienols in preneoplastic mammary epithelial cells.
Sylvester PW, Nachnani A, Shah S, Briski KP.
College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209-0470, USA. pysylvester@ulm.edu
Tocotrienols are a subclass of vitamin E compounds that display potent anticancer activity. Determining the anticancer mechanism of action of tocotrienols will provide essential information necessary for understanding the potential health benefits of these compounds in reducing the risk of breast cancer in women. Epidermal growth factor (EGF) is a potent mitogen for normal and neoplastic mammary epithelial cells. Initial events in EGF-receptor (EGF-R) mitogenic-signalling are G-protein activation, stimulation of adenylyl cyclase and cyclic AMP (cAMP) production. Studies were conducted to determine if the antiproliferative effects of tocotrienols are associated with reduced EGF-induced G-protein and cAMP-dependent mitogenic signalling. Preneoplastic CL-S1 mouse mammary epithelial cells were grown in culture and maintained on serum-free media containing 0-25 micro mol/L tocotrienol-rich fraction of palm oil and/or different doses of pharmacological agents that alter intracellular cAMP levels. Tocotrienol-induced effects on EGF-receptor levels of tyrosine kinase activity, as well as EGF-dependent mitogen-activated pathway kinase (MAPK) and Akt activation, were determined by western blot analysis. Results demonstrate that the antiproliferative effects of tocotrienols in preneoplastic mammary epithelial cells do not reflect a reduction in EGF-receptor mitogenic responsiveness, but rather, result from an inhibition in early post-receptor events involved in cAMP production upstream from EGF-dependent MAPK and phosphoinositide 3-kinase/Akt mitogenic signalling. In summary, these data further characterise the mechanism of action of tocotrienols in suppressing preneoplastic mammary epithelial cell proliferation, and advance the current understanding of the potential health benefits of these compounds in reducing the risk of breast cancer in women.
PMID: 12492634 [PubMed - indexed for MEDLINE]
Effect of palm oil carotene on breast cancer tumorigenicity in nude mice.
Nesaretnam K, Radhakrishnan A, Selvaduray KR, Reimann K, Pailoor J, Razak G, Mahmood MM, Dahliwal JS.
Malaysian Palm Oil Board, Bandar Baru Bangi, Selangor. sarnesar@mpob.gov.my
Biological therapies are new additions to breast cancer treatment. Among biological compounds, beta-carotene has been reported to have immune modulatory effects, in particular, enhancement of natural killer cell activity and tumor necrosis factor-alpha production by macrophages. The objective of this study was to investigate the effect of palm carotene supplementation on the tumorigenicity of MCF-7 human breast cancer cells injected into athymic nude mice and to explore the mechanism by which palm carotenes suppress tumorigenesis. Forty-eight 4-wk-old mice were injected with 1 x 10(6) MCF-7 cells into their mammary fat pad. The experimental group was supplemented with palm carotene whereas the control group was not. Significant differences were observed in tumor incidence (P< 0.001) and tumor surface area and metastasis to lung (P< 0.005) between the two groups. Natural killer (NK) cells and B-lymphocytes in the peripheral blood of carotene-supplemented mice were significantly increased (P < 0.05 and P < 0.001, respectively) compared with controls. These results suggest that palm oil carotene is able to modulate the immune system by increasing peripheral blood NK cells and B-lymphocytes and suppress the growth of MCF-7 human breast cancer cells.
PMID: 12120953 [PubMed - indexed for MEDLINE]
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Differences in all-cause, cardiovascular and cancer mortality between Hong Kong and Singapore: role of nutrition.
Zhang J, Kesteloot H.
Department of Epidemiology, School of Public Health, Catholic University of Leuven, Belgium.
BACKGROUND: The majority of inhabitants in Hong Kong and Singapore are ethnic Chinese, but all-cause and cardiovascular mortality rates in these two regions are markedly different. This study describes differences in the magnitude and trends in mortality and attempts to explain these differences. METHODS: Data of mortality rates in 1963-1965 and 1993-1995 in the age class of 45-74 years, dietary habits and other factors were compared between Hong Kong and Singapore using Japan, Spain and the USA as reference countries. Mortality and food consumption data were obtained from WHO and FAO, respectively. RESULTS: Large differences in all-cause and cardiovascular mortality exist between Hong Kong and Singapore. The difference in total cancer mortality was less consistent and smaller. The most pronounced finding was that ischemic heart disease mortality in 1993-1995 was 2.98 and 3.14 times higher in Singapore than in Hong Kong in men and women, respectively. Of the five countries considered, Singapore has the highest all-cause mortality in both sexes in the period of 1960-1995. The ratio of animal to vegetal fat was higher in Singapore (2.24) than in Hong Kong (1.08). Singapore had higher serum concentrations of total cholesterol and low-density lipoprotein cholesterol than Hong Kong, but the opposite result was observed for high-density lipoprotein cholesterol. CONCLUSIONS: There are striking differences in all-cause and cardiovascular mortality between Hong Kong and Singapore. These differences can be most reasonably and plausibly explained by their differences in dietary habits, for example, a higher consumption of coconut and palm oil, mainly containing saturated fat, in Singapore.
PMID: 11855581 [PubMed - indexed for MEDLINE]
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An assessment of the carcinogenic potential of shea oleine in the rat.
Carthew P, Baldrick P, Hepburn PA.
Safety & Environmental Assurance Centre, Unilever Research, Colworth House, Sharnbrook, Bedfordshire MK41 6EP, UK. philip.carthew@unilever.com
Shea oleine, an oil fraction derived from the nut of the tree Butyrospermum parkii, is used as a frying oil. As part of a series of studies, this investigation examined the carcinogenic potential of 15% (w/w) shea oleine in comparison with 15% (w/w) sheanut oil, and palm oil following dietary administration to rats over 104 weeks. The assessment comprised an evaluation of mortality, clinical signs, body weight, food intake, clinical pathology, organ weights and macroscopic and histopathological examination plus tumour type and incidence evaluation. Results showed that shea oleine produced no adverse effects and no evidence of tumorigenic potential compared to other commercially available sheanut and palm oils in the rat. Notable differences were confined to reduced body weight gain and food intake, reduced cholesterol and increased alkaline phosphatase levels, reduced heart weight and an increased incidence of pulmonary lipidosis with shea oleine diets. The latter effect may reflect a naturally lower incidence of this finding with palm oil diets. Tumour findings, specific to shea oleine diets, were restricted to an increase in the number of hepatomas for females, pancreatic exocrine adenomas for males and skin keratoacanthomas for males fed shea oleine diets. The increase in the incidence of hepatomas with treatment was thought to be related to the high fat content of the diets. The incidence of these tumour findings was similar to that given in published data for the Wistar rat, or the 'in house' values for tumour incidence in rats fed high-fat diets. In conclusion, none of the findings in this study were considered to be adverse effects. In comparison with other commercially available edible oils, shea oleine showed no tumorigenic potential following dietary administration at 7.5 g/kg/day in the rat.
PMID: 11434988 [PubMed - indexed for MEDLINE]
The effect of dietary carotenoids on lung tumorigenesis induced by intratracheally instillated diesel exhaust particles.
Yamanushi TT, Ichinose T, Seto H, Sagai M, Torii MI, Igarashi O.
Institute of Environmental Science for Human Life, Ochanomizu University, Tokyo, Japan.
The purpose of this study is to examine the carotenoid effects on lung tumorigenesis induced by intratracheal instillation of diesel exhaust particles (DEP) into mice weekly for 20 wk. It was suggested that active oxygen radicals might play an important role in DEP-induced lung tumorigenesis. Mice were divided to 4 groups of diet containing 0.02% of palm oil carotene, 0.02% of beta-carotene, or no carotenoid with or without DEP. The BF group (4% fat) and the HF group (16% fat) were prepared for each diet group. The experimental period was 12 mo. By the administration of palm oil carotene, neither adenocarcinoma nor adenoma was found in the BF group. In the HF group with palm oil carotene, no adenocarcinoma was observed, and adenoma was reduced. Adenoma in the HF group was not greatly reduced by beta-carotene, but rather increased in the BF group. No adenocarcinoma was found in either the BF or the HF groups with beta-carotene. The 8-hydroxydeoxyguanosine/deoxyguanosine ratio in palm carotene groups was lower than in the other groups, while that in beta-carotene groups was not. From these results, palm oil carotene was suggested to prevent lung tumorigenesis by its protective effect on DNA from active oxygen. Beta-carotene was supposed to have different effects from palm oil carotene on lung tumorigenesis. Besides the chemopreventive effect, the growth of mice was inhibited by the administration of palm oil carotene. Further studies are necessary to elucidate the mechanisms of carotenoid effects.
PMID: 11349888 [PubMed - indexed for MEDLINE]
Tocotrienols inhibit growth of ZR-75-1 breast cancer cells.
Nesaretnam K, Dorasamy S, Darbre PD.
Palm Oil Research Institute of Malaysia, PO Box 10620, Kuala Lumpur 50720, Malaysia.
The vitamin E component of palm oil provides a rich source of tocotrienols which have been shown previously to be growth inhibitory to two human breast cancer cell lines: responsive MCF7 cells and unresponsive MDA-MB-231 cells. Data presented here shows that the tocotrienol-rich fraction (TRF) of palm oil and individual fractions (alpha, gamma and delta) can also inhibit the growth of another responsive human breast cancer cell line, ZR-75-1. At low concentrations in the absence of oestrogen tocotrienols stimulated growth of the ZR-75-1 cells, but at higher concentrations in the presence as well as in the absence of oestradiol, tocotrienols inhibited cell growth strongly. As for MCF7 cells, alpha-tocopherol had no effect on growth of the ZR-75-1 cells in either the absence or presence of oestradiol. In studying the effects of tocotrienols in combination with antioestrogens, it was found that TRF could further inhibit growth of ZR-75-1 cells in the presence of tamoxifen (10(-7) M and 10(-8) M). Individual tocotrienol fractions (alpha, gamma, delta) could inhibit growth of ZR-75-1 cells in the presence of 10(-8) M oestradiol and 10(-8) M pure antioestrogen ICI 164,384. The immature mouse uterine weight bioassay confirmed that TRF could not exert oestrogen antagonist action in vivo. These results provide evidence of wider growth-inhibitory effects of tocotrienols beyond MCF7 and MDA-MB-231 cells, and with an oestrogen-independent mechanism of action, suggest a possible clinical advantage in combining administration of tocotrienols with antioestrogen therapy.
PMID: 11271861 [PubMed - indexed for MEDLINE]
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Oxidative damage to mitochondria in normal and cancer tissues, and its modulation.
Kamat JP, Devasagayam TP.
Cell Biology Division, Bhabha Atomic Research Centre, Mumbai, India.
Cellular damage induced by reactive oxygen species (ROS) in normal tissues has been implicated in the etiology of several human ailments. Among the subcellular organelles, damage to mitochondria is considered crucial and can lead to cytotoxicity and cell death. However, the same damage, if it is selectively induced in cancer tissues can lead to its cure. Hence analyzing the mechanisms of such damage and its modulation may result in better prevention or cure. Using mitochondria derived from rat brain/liver as well as sarcoma 180 ascites cells, we have examined the mechanisms of damage to lipid, as assessed by different products of lipid peroxidation and to proteins, as determined by loss of enzyme activity and protein oxidation. Mechanisms involved, in terms of scavenging of ROS have been determined using pulse radiolysis for hydroxyl radical and histidine destruction assay for singlet oxygen. Various ROS were generated using gamma-radiation, photosensitization etc. under different conditions. Some novel porphyrins, with potential uses in photodynamic therapy also were used as photosensitizers. Our study shows that ROS can induce significant oxidative damage in mitochondria from both normal and tumor tissues and this can be inhibited by natural antioxidants like tocotrienols, nicotinamide and caffeine. Damage, on the other hand, can be enhanced by deuteration of the buffer and oxygenation. Our results hence demonstrated that mitochondria were sensitive to damage by ROS and its modulation may have potential uses in prevention of the disease in normal tissues; if damage can be selectively induced in tumor, it can lead to its regression.
PMID: 11154799 [PubMed - indexed for MEDLINE]
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Chemistry and biochemistry of palm oil.
Sambanthamurthi R, Sundram K, Tan Y.
Palm Oil Research Institute of Malaysia, PO Box 10620, 50720, Kuala Lumpur, Malaysia.
Publication Types:
PMID: 11106812 [PubMed - indexed for MEDLINE]
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