phytosterols and Colonic-Neoplasms

Substantial attention has been given to primary cancer prevention in daily life. Dietary factors are through to contribute to as much as one-third of the factors influencing the development of cancer. Ones of the components of a plant-based diet are beta-sitosterol and taraxasterol, compounds attracting our specific attention. This review summarizes the biological activities of presented phytosterols (anti-inflammatory, cholesterol-lowering, anti-microbial, anti-bacterial, anti-fungal effects). Our interest has been focussed especially on their anti-tumor and chemopreventive activity. They have been shown experimentally to inhibit colon and breast cancer development. They act at various stages of tumor development, including inhibition of tumorigenesis, inhibition of tumor promotion, and induction of cell differentiation. They effectively inhibit invasion of tumor cells and metastasis. With regard to toxicity, no obvious side effects of phytosterols have been observed in studies to date, with the exception of individuals with phytosterolemia. The exact mechanism by which dietary phytosterols act is not fully understood. However, some mechanisms have been offered. Therefore, they have a bright future in clinical application. Further investigation to explore their potential in tumor treatment may prove to be worthwhile.

Topics: Animals; Anti-Inflammatory Agents; Anticarcinogenic Agents; Antineoplastic Agents; Antioxidants; Breast Neoplasms; Colonic Neoplasms; Diet; Drugs, Chinese Herbal; Female; Humans; Phytosterols; Sitosterols; Sterols; Triterpenes

High serum LDL cholesterol concentration is a major risk factor for cardiovascular complications. This risk can be lowered by diet. In this respect foods containing plant sterol or stanol esters can be useful for mildly- and hypercholesteraemic subjects. Plant sterols and stanols, which are structurally related to cholesterol, decrease the incorporation of dietary and biliary cholesterol into micelles. This lowers cholesterol absorption. Furthermore, these components increase ABC-transporter expression, which may also contribute to the decreased cholesterol absorption. Consequently, cholesterol synthesis and LDL receptor activity increase, which ultimately leads to decreased serum LDL cholesterol concentrations. Animal studies have further shown that these dietary components may also lower atherosclerotic lesion development. Plant sterols and stanols also lower plasma lipid-standardized concentrations of the hydrocarbon carotenoids, but not those of the oxygenated cartenoids and tocopherols. Also, vitamin A and D concentrations are not affected. Although absorption of plant sterols and stanols (0.02-3.5%) is low compared to cholesterol (35-70%), small amounts are found in the circulation and may influence other physiological functions. However, there is no consistent evidence that plant sterols or stanols can change the risk of colon or prostate cancer, or immune status. In conclusion, plant sterols and stanols effectively reduce serum LDL cholesterol and atherosclerotic risk. In addition potential effects of plant sterols and stanols on other metabolic processes remain to be elucidated.

Topics: Animals; Anticholesteremic Agents; Antioxidants; Arteriosclerosis; Cholesterol; Colonic Neoplasms; Diet; Humans; Immunity; Intestinal Absorption; Male; Phytosterols; Prostatic Neoplasms

Epidemiological and experimental studies have shown that increased intake of plant foods and decreased meat consumption are correlated with a decreased risk for colon cancer. Many components of plant foods are suggested to mitigate colon carcinogenesis, including vitamins, minerals, and dietary fiber. Phytosterols are a common component of plant foods consumed in relatively large quantities by vegetarians, who are at lower risk for colon cancer development than individuals on a Western diet low in phytosterols. In addition, phytosterols have been shown experimentally to inhibit colon cancer development. Dietary cholesterol, although structurally similar to the phytosterols, is correlated etiologically to the incidence of colon cancer, with changes in serum cholesterol levels and fecal bile acid profiles suggested to increase susceptibility to colon tumorigenesis. The objective of this paper is to discuss the effect of dietary phytosterols on cholesterol and bile acid metabolism and how these effects may lead to a decreased risk for colon cancer development.

Topics: Animals; Bile Acids and Salts; Cholesterol; Colonic Neoplasms; Food Analysis; Humans; Mice; Phytosterols; Rats

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; bcl-2-Associated X Protein; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Datura; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Phytosterols; Plant Extracts; Proto-Oncogene Proteins c-bcl-2; Structure-Activity Relationship

Plant sterols in their free forms are known to inhibit colon cancer. Whether these activities persist when compounds are incorporated into processed food is not reported yet. This study aimed to test the ability of plant sterol esters (PSE) incorporated into a nonpuffed extruded food (NPE) model to inhibit colon carcinogenesis. PSE was added into NPE at four concentrations (0.0%, 0.7%, 1.4%, and 2.1%). PSE-NPE activity was tested in azoxymethane/dextran sodium sulfate-induced Balb/c mice. The groups given PSE-NPE did not show any colon tumor formation. Immunohistochemistry results revealed that the group fed with 1.4% PSE had the lowest histoscore for cyclooxygenase-2 expression and the highest histoscore for cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9expressions. The results of this study indicated that even after incorporation into a food system, which is processed using high pressure and temperature, PSE retained its chemopreventive activity. The proposed mechanisms are by suppressing inflammation and inducing apoptosis.

Topics: Animals; Apoptosis; Caspase 3; Caspase 8; Colon; Colonic Neoplasms; Cyclooxygenase 2; Esters; Humans; Male; Mice; Mice, Inbred BALB C; Phytosterols

Consumption of whole grains has been reported to be associated with a lower risk of colorectal cancer. Recent studies illustrated that phytochemicals in wheat bran (WB) may protect against colorectal cancer. There is a growing interest in the phytosterol contents of foods as either intrinsic or added components due to their beneficial health effects. However, little is known whether phytosterols in WB contribute the observed chemopreventative activity of the grain. In the present study, we directly purified and identified four oxyphytosterols 1-4 from sterol-enriched fraction of WB, and also successfully synthesized five sterol oxides 5-8 and 13. Using these nine compounds as references, we outlined a comprehensive profile of steroids in WB using tandem liquid chromatography mass spectrometry with electrospray ionization (LC-ESI/MS(n), n = 2-3) techniques for the first time. Among them, three sterol oxides 13, 14, and 18 are novel compounds, and 14 compounds 3, 4, 6-11, 13, 14, 16, and 18-20 were reported in WB for the first time. Our results on the inhibitory effects of available sterol oxides 1-8 and 13 against the growth of human colon cancer cells HCT-116 and HT-29 showed that compounds 2-8 exerted significant antiproliferative effects, with oxysterol 8 being the most active one in both cells. We further demonstrated that four most active sterol oxides 5-8 could induce cell death through the apoptosis pathway. Our results showed that phytosterols, particularly oxyphytosterols, in WB possess significant antiproliferative properties, and thereby may greatly contribute the observed chemoprevention of the whole grain wheat.

Topics: Anticarcinogenic Agents; Apoptosis; Cell Proliferation; Colonic Neoplasms; Dietary Fiber; HCT116 Cells; HT29 Cells; Humans; Mass Spectrometry; Molecular Structure; Phytosterols; Plant Extracts

Liver X receptors (LXRα and LXRβ) are members of the nuclear receptor family and are important regulators of cholesterol, fatty acid, and glucose homeostasis. LXR agonists are effective for treatment of murine models of atherosclerosis, diabetes, and Alzheimer's disease. Recently we and other groups observed that LXR agonists suppressed proliferation of multiple human cancer cell lines in vitro as well as suppressed the growth and progression of prostate tumor xenografts in nude mice. LXR agonists appear to cause G1 cell cycle arrest in cancer cells by reducing the protein expression level of Skp2, cyclin A2, cyclin D1, and the phosphorylation of Rb, while increasing the protein expression level of cell cycle inhibitor p27(Kip1) and p53. LXR agonist also suppressed the oncogenic activity of β-catenin, an important regulator in Wnt signaling, as well as the proliferation in human colon cancer cells. Phytosterols, the plant equivalent of mammalian cholesterol, have been shown to be agonists for LXRs. Intake of phytosterol-rich diets reduced the incidence of colon cancer. We therefore propose that activation of LXR signaling via treatment with LXR agonists or intake of phytosterols-rich diets can reduce the incidence and suppress the tumor growth of colon cancer.

Topics: Animals; Cell Cycle; Colonic Neoplasms; Disease Models, Animal; Humans; Liver X Receptors; Male; Mice; Mice, Nude; Models, Theoretical; Neoplasm Transplantation; Orphan Nuclear Receptors; Phosphorylation; Phytosterols; Signal Transduction; Wnt Proteins

The effects of physiological dietary phytosterol supplements on intestinal microflora activity and faecal sterols and their capacity to protect rats fed a normal or high saturated fatty-acid diet against tumour development were studied. A group of 80 female Wistar rats were fed an 8% lipid diet for 4 weeks (adaptation period) and then randomly assigned in a factorial experimental design study to diets containing 8% or 24% hydrogenated coconut oil, with or without a 24-mg/day/rat phytosterol supplement. They were instilled intrarectally with saline or methyl-nitroso-urea (MNU). Faecal sterol output was analysed for one week each month. Pathological analysis was done at the end of the 30-week experiment. Animals treated with MNU and given phytosterol supplements had tumour frequencies (8/20) similar to those not fed phytosterols (11/20). The fat-supplemented diet had no significant influence. Colonic glands were found in area of lymphoid follicles in all the groups, but were more frequent in rats on high-fat diets (P < 0.01). The coprostanol and the cholesterol excretion of the phytosterol-supplemented rats was significantly enhanced. Therefore phytosterols have an unfavourable effect on bacterial activity. These data confirm the capacity of phytosterols to decrease cholesterol absorption, but indicate that a large excess of phytosterol must be avoided until further research on its effects on carcinogenesis has been done.

Topics: Animals; Anticarcinogenic Agents; Cholestanol; Cholesterol; Colonic Neoplasms; Dietary Fats; Disease Models, Animal; Feces; Female; Intestinal Mucosa; Phytosterols; Rats; Rats, Wistar; Time Factors

Work from our laboratory, as well as others, suggests a protective role of phytosterols (PS), especially beta-sitosterol, from colon, prostate, and breast cancer. Asians and vegetarians consume higher amounts of PS than Western societies. The latter societies have a higher incidence of these cancers than Asians and vegetarians. The aim of this study was to evaluate peanuts and its products as sources of PS in the American diet. Roasted peanuts contain 61-114 mg PS/100 g depending on the peanut variety, 78-83% of which is in the form of beta-sitosterol. Unrefined peanut oil contains 207 mg PS/100 g, which is similar to that of the US Department of Agriculture Nutrient Database. This value is higher than that of unrefined olive oil. Refining these oils results in reduction in PS concentration in the oil. This loss is greater in the case of olive oil than peanut oil. Further refining, such as deodorization, results in significant loss in PS, but hydrogenation after refining has a minimal effect on PS loss. Peanut butter, which represents 50% of the peanuts consumed in the United States, contains 144-157 mg PS/100 g. Peanut flour, which results from partial removal of oil from peanuts, contains 55-60 mg PS/100 g. The data suggest that peanuts and its products, such as peanut oil, peanut butter, and peanut flour, are good sources of PS.

Topics: Antineoplastic Agents; Arachis; Breast Neoplasms; Colonic Neoplasms; Female; Humans; In Vitro Techniques; Male; Phytosterols; Phytotherapy; Prostatic Neoplasms; Sitosterols

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Bile Acids and Salts; Cell Cycle; Cell Division; Chenodeoxycholic Acid; Cholesterol; Cholic Acid; Cholic Acids; Colon; Colonic Neoplasms; Colonic Polyps; Deoxycholic Acid; Feces; Female; Humans; Lithocholic Acid; Male; Middle Aged; Phytosterols; Rectum; Sterols

Cholesterol and fat are implicated as dietary factors enhancing the risk for colon carcinogenesis. Plant sterols such as beta-sitosterol when added to diets of experimental animals treated with colon carcinogens reduce tumor yields and counteract the proliferative changes associated with carcinogenesis. The question of whether the diet of human populations at low risk for colon cancer is mirrored in their sterol composition is addressed in this study. Four study groups consisting of 18 Seventh-day Adventist (SDA) pure vegetarians, 50 SDA lacto-ovo vegetarians, 50 SDA nonvegetarians, and 50 general population nonvegetarians were selected from the greater Los Angeles basin, and 3-day composite diets were analyzed for their sterol composition. The most significant index of dietary sterol status is the ratio, beta-sitosterol + stigmasterol/cholesterol (plant sterol/cholesterol ratio). The values for the four groups ranged from 0.49 to 16.0 (general population nonvegetarians = 0.49; SDA-nonvegetarians = 0.98; SDA lacto-ovo vegetarians = 3.26; SDA pure vegetarians = 16.0). The data also show that the absolute amounts of cholesterol consumed as a factor by itself might not be as significant as its relationship to total plant sterols in the diet.

Topics: Adult; Age Factors; Cholesterol, Dietary; Colonic Neoplasms; Diet; Diet, Vegetarian; Energy Intake; Female; Humans; Male; Middle Aged; Phytosterols; Sex Factors; Sitosterols; Stigmasterol