Introduction

Phytosterols (plant sterols and stanols) are like cholesterol steroid alcohols (trit-erpenes). They are the equivalent of cholesterol in mammalian species and resemble cholesterol both in structure and biological function. They are essential * Both authors contributed equally to this work. structural components of the cell membrane, where they regulate membrane fluidity and permeability as well as membrane-associated metabolic processes. Phytosterols present a diverse group of more than 200...

Pathogenesis Of Cancer Acquired Capabilities

Research over the past 25 years has produced a deeper understanding of the molecular, biochemical, and cellular changes that occur as cells are transformed from normal cells to malignant cancers. The multiple genetic defects leading to cancer cell production can result from exposure to environmental, dietary, and lifestyle factors, as well as infectious agents. The multistep, multistage process of gradual carcinogenetic changes in the biological behavior of a clonogenic population of cells is...

Alcoholassociated Carcinogenesis

28.2.1 Increased Generation of Acetaldehyde Acetaldehyde is probably the most important single mechanism through which alcohol contributes to increased cancer risk.4 Acetaldehyde is produced as a metabolite from ethanol by the action of cellular alcohol dehydrogenase (ADH), mainly in the liver, but also in peripheral tissues and through the action of bacterial ADH in the colon and saliva.5 Acetaldehyde is highly reactive and binds rapidly to cellular proteins as well as to DNA, resulting in...

Peter G Bradford and Atif B Awad Contents

12.1 Dietary Phytosterols 12.2 Dietary Phytosterols and Cancer Epidemiological Studies 253 12.3 Dietary Phytosterols and Cancer Animal Experimentation Studies 255 12.3.1 Colon 12.3.2 Breast and Prostate 12.4 Dietary Phytosterols and Cancer Mechanisms of Action 258 12.4.1 Effects on 12.4.2 Effects on Cholesterol 12.4.3 Effects on Cell 12.4.4 Effects on Membrane-Bound 12.4.5 Effects on Models of Tumor 12.4.6 Effects on Immune 12.4.7 Estrogenic 12.4.8 Effects on Membrane 12.1 DIETARY PHYTOSTEROLS...

Table 112

Phytosterol Contents of Typical Foods Olive oil (extra virgin) 144-150 Vegetable oil margarine, full-fat 310 Vegetable oil margarine, half-fat 140 Apples, banana, grapefruit, melons, kiwi, orange, peach, 1.3-44 pear, pineapple Source Data from References 8, 11, 13, and 14. 85 P-sitosterol, about 8 to 15 sitostanol, 5 to 10 campesterol, and a number of minor sterols and stanols at low concentrations (< 1.5 each). Stanols are obtained by hydrogenation of plant sterols. 11.4 DIETARY INTAKE OF...

Mechanisms By Which Flavonoids Inhibit Tumor Metastasis

Cancer mortality is primarily due to metastasis. In order for cancer cells to metastasize they must be able to degrade the basement membrane (BM), traverse the extracellular matrix (ECM), enter the lymphatic or vascular system, adhere to a distant site, and then invade the local tissue. BM and ECM are composed of several proteins with type IV collagen the major structural component. Penetration of BM and ECM by cancer cells through proteolytic degradation has been suggested to be the first step...

Info

Studies have also used EGCG as a major tea bioactive compound. In addition, EGCG-rich green tea polyphenol extract and whole tea have been used in some animal studies. 16.2.1.1 Effects of Tea Polyphenols on Invasion and Metastasis of Melanoma A series of studies has been conducted to determine the anti-invasion activities in vitro and antimetastasis activities in vivo of tea polyphenols, especially EGCG, in several cancer types. Because of the highly metastatic potential of melanoma cells, the...

Clinical Trials With Retinoids

Acute promyelocytic leukemia (APL) shows the most spectacular response to retinoid treatment, consistent with results in the cultured human APL cell line HL60.35 Combined therapy with RA and conventional chemotherapy produces 70 long-term remission.36 A few cases of APL develop resistance to RA therapy. In contrast, although RA alone has spectacular initial effects on patients with the form of APL that involves the t(15,17)-translocation, which produces the fusion protein PML-RARa, many of...

Beyond Radical Scavenging

20.3.1 Direct Protection against DNA Damage Studies investigating hydrogen peroxide-induced toxicity in cell culture determined that the anthocyanins delphinidin and cyanidin (aglycones and glycosides) were protective against DNA strand breaks in human colon cells.6970 Furthermore, glycosides of cyanidin, petunidin, peonidin, and malvidin were observed to decrease the formation of oxidized DNA bases and lipid hydroperoxides in vitamin E-deficient rats.71 Although the mechanisms mediating these...

Bioactive Dietary Components

All classical nutrient categories consist of bioactive dietary components, including carbohydrates, amino acids, fatty acids and structural lipids, minerals, and vitamins. In addition is an extensive list of non-nutrient components, particularly phytochemicals, which can have anticancer activity. Phytochemicals are components of a plant-based diet that possess substantial anticarcinogenic and antimu-tagenic properties.7 An estimated 25,000 different chemical compounds occur in fruits,...

Sterol Nomenclature

Phytosterols are products of the isoprenoid biosynthesis pathway and like cholesterol are synthesized from acetyl coenzyme A via squalene involving more than 30 enzyme-catalyzed reactions all taking place in plant cell membranes.1 Similar to cholesterol, phytosterols serve as precursors for plant steroid hormones, so called brassinosteroids.2 Phytosterols are found in various plants and marine sources.3 They all have a steroid nucleus, a hydroxyl group at carbon 3 in the P-position and a double...

Critical Issues And Future Directions In Research On Flavonoids And Tumor Metastasis

Previous research has indicated that flavonoids such as tea polyphenols, soy isoflavones, apigenin, and quercetin have significant anti-invasion activities in vitro associated with inhibition of angiogenesis, proteolytic enzymes activities, and enhancement of cell-ECM interactions. Some in vitro anti-invasion activities of flavonoids are confirmed in animal models. These studies suggest that some flavonoids may play a significant role in prevention of cancer metastasis, in addition to...

Pariza 2001 Birds Behaviour

Inhibition of carcinogenesis by conjugated linoleic acid potential mechanisms of action. J Nutr 2002 132 2995-2998. 2. Pariza MW. Perspective on the safety and effectiveness of conjugated linoleic acid. Am J Clin Nutr 2004 79 1132S-1136S. 3. Chin SF, Liu W, Storkson JM, Ha YL, Pariza MW. Dietary sources of conjugated dienoic isomers of linoleic acid, a newly recognized class of anticarcinogens. J Food Compos Anal 1992 5 185-197. 4. Ma DW, Wierzbicki AA, Field CJ, Clandinin MT....

Mammographic Density and Breast Cancer

Epithelium and stromal tissues that are strongly related to risk of breast cancer appear radiologically dense, whereas fat appears radiologically lucent.93 The proportion of the mammographic image occupied by radiologically dense tissue is a composite measure of breast tissue composition. At present, the role of mammographic density in breast cancer etiology is not clear.94 However, it has been established that mammographic density is an independent predictor of breast cancer risk, with...

Vitamin A And Cancer In Experimental Animals

Vitamin A has long been associated with decreased cancer incidence in animals, especially of epithelial cancers. This concept was promoted by early insights into the effects of vitamin A depletion on animals. Wolbach16 published studies in 1925 demonstrating that vitamin A deficiency resulted in squamous metaplasia and correlated with increased respiratory and upper alimentary canal cancer. Studies with laboratory animals, prompted by these early observations, revealed the conversion of mucous...

Antioxidant Activity

Anthocyanins are highly reactive radical scavengers in various in vitro environments. Anthocyanins not only scavenge radicals, but through their ability to bind heavy metals such as iron, zinc, and copper, also prevent the formation of radicals.47 Anthocyanins may also exert antioxidant abilities through the protection or enhancement of endogenous antioxidants (i.e., sparing effect), or through the induction of antioxidant enzymes such as glutathione-S-transferase (GST) and superoxide dismutase...

Biochemical And Molecular Mechanisms Of Cancer Chemoprevention By Catechins

The development of genetic oncology has demonstrated that damage to numerous regulatory genes may result in induction of invasive and metastatic cancer. It has been established that the pathological processes of multistep carcinogenesis comprises initiation, promotion, and progression.7 The natural history of carcinogen-esis and cancer development provides a strong rationale for a preventive approach to the control of this disease and leads one to consider the possibility of active...

Underlying Chemopreventive Mechanisms Of Vitamin C

Clinical trials involving high dosages of dietary vitamin C supplements do not support a cancer protective role for vitamin C.4445 However, there is suggestion for such a role from epidemiological and observational studies based on food intake.646 There was early epidemiologic evidence that a high intake of vitamin C-rich fruits and vegetables as well as a high serum level of vitamin C is inversely associated with the risk of some cancers. In 1991, Henson et al.46 analyzed 46 epidemiologic...

Mode Of Action Of Types Of Dietary Fats Against Colon Cancer

Successful approach for implementation of preventive strategies depends on a mechanistic understanding of carcinogenesis at the tissue, cellular, and molecular levels. Carcinogenesis is typically a slow, chronic process and the development of invasive disease is characterized by molecular derangements. Although the molecular mechanisms by which n-3 PUFAs inhibit colon carcinogenesis have not been fully elucidated, several putative mechanisms of action have been proposed for colon cancer...

References

Flavonoid antioxidants. Curr Med Chem 2001 8(7) 797-807. 2. Middleton E. Biological properties of plant flavonoids an overview. Int J Pharmacognosy 1996 34 344-348. 3. Harborne JB, Williams CA. Advances in flavonoid research since 1992. Phy-tochemistry 2000 55(6) 481-504. 4. Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radical Biol Med 1996 20(7) 933-956. 5. Rice-Evans C. Plant polyphenols free radical...

Introduction Cancer Epidemiology

Cancers represent a heterogeneous group of diseases characterized by uncontrolled growth and spread of abnormal cells in the body. The disruptive behaviors of cancer cells reflect dynamic changes in their genomes and in gene expression that result in disruption of normal regulatory signaling circuits. Cancers vary on the basis of both the biologic features of the disease and the characteristics of the affected organism. The process by which normal cells are transformed into cancer cells is...

Selenium Metabolism In Tissue Culture Models

Present research efforts are primarily focused on the mechanism of cancer reduction by selenium, and tissue cultures have been used advantageously to study how tumors are reduced by this element. Research with mouse mammary epithelial cells indicate that the beta-lyase mediated production of a monomethylated selenium metabolite, namely, methylselenol, from SeMCYS is a key step in cancer chemoprevention by this agent.78 In order for SeMCYS to be effective, cells must possess this beta-lyase. One...

ATOS

Functional Signalling Hydrophobic Domain Domain Domain Responsible for Affects Mediates docking in redox apoptotic PP2A PKC membranes and FIGURE 6.1 Major domains in VE analogs. Shown are the structures of a-TOH and a-TOS with the specification and major function of the three main domains. Domains I and II are identical Domain III differs. While Domains I and II are important for the extent of the activity, Domain III determines whether the agent does or does not induce apoptosis. important to...

Resveratrolinduced Cancer Cell Apoptosis

Resveratrol induces apoptosis of diverse leukemia and epithelial cancer cell lines. Leukemia cells subject to resveratrol-induced apoptosis include early myeloid (K562, KCL22, HL60), monocytic (U937, THP1), B-lymphoid (WSU-CLL), and T-lymphoid (Jurkat).141920 Human carcinoma cell lines that apoptose in response to resveratrol span human breast cancer (MCF-7), prostate cancer (LNCaP, DU145), colorectal cancer (SW480), pancreatic cancer (PANC-1, AsPC-1), and esophageal cancer (Bic-1, Seg-1,...

Selenocompounds In Plants And Animals

The metabolism of selenocompounds and distribution of selenium on a worldwide basis have been presented.3-7 As much as 80 of the total selenium in some accumulator plants is present as SeMCYS, which until recently was thought to be absent in nonaccumulator plants. Selenocompounds present in plants may have a profound effect on the health of animals and humans. The total selenium content cannot be used as an indication of its efficacy but the knowledge of individual selenocompounds is critical...

Mechanisms Of Cancer Reduction By Selenium

A number of reviews have been written on the chemopreventive effects of selenium including most recently those by Combs and Gray,71 Ganther,86 Ip,57 Schrau-zer,49 El-Bayoumy,87 and Fleming et al.88 An entire volume of Nutrition and Cancer was devoted to selenium and cancer in honor of the late Larry Clark.89 The mechanism for selenium as an anticarcinogenic element is not known but several speculations have been advanced. It is well established that the most effective dose of selenium for...

Molecular Mechanisms Of Action Of Isoflavones

14.4.1 Regulation of the Expression of Genes Related to Cell Cycle and Apoptosis To explore the molecular mechanisms by which genistein induces cell cycle arrest, we have examined the expression of cell cycle-related genes including cyclins, CDC2, and cyclin dependent kinase inhibitors (CDKIs). Our results showed that the treatment of cells with different concentrations of genistein caused a dose-dependent decrease in the expression of cyclin Bj,50,66 corresponding with the G2 M phase cell...

Increased Response to Antigrowth Signals and Induction of Differentiation

Normal cells within tissues are also responsive to antiproliferative signals that serve to maintain cellular quiescence and tissue homeostasis. These antigrowth signals are soluble factors or inhibitors embedded in the extracellular matrix. Signals are transmitted to the nucleus via intracellular signaling circuits that are in a balance with the positive growth signals. One of the most prominent negative growth signals in many cell types is TGF-P).26 Most antigrowth signals act on the tumor...

A25OH2D3 Analogs In The Treatment Of Cancer

In addition to its well-established effects on the regulation of calcium homeo-stasis, 1a,25-(OH)2D3has potent regulatory effects on cell growth and differentiation. Experimental evidence suggests a role for 1a,25-(OH)2D3 in tumor cell killing, anti-angiogenesis, and interference with tumor cell invasion, thus making it a potential candidate agent for cancer regulation. 1a,25-(OH)2D3 has been recognized for its regulatory effects on cell cycle checkpoints in several cell types. It has a major...

Ho

FIGURE 5.1 Nutritional forms of vitamin D. the factors that may influence an individual's vitamin D status are latitude of the residence, customs of dress, and extent of indoor residency and lack of outdoor activity,9-11 According to Clemens et al.,12 the extent and efficiency of vitamin D synthesis are dependent on the character of the skin. Skin with high melanin content, such as darker skin, requires much longer exposure to sunlight to achieve the same level of vitamin D synthesis as...

Mechanisms

Several mechanisms have been suggested regarding how lignans may achieve their protective effects on breast cancer. Due to the structural similarities between lignans and estrogens, it has been hypothesized that the lignans may interfere and or interact with endogenous estrogen by altering estrogen bioavailability, modulating estrogen synthesis, and altering estrogen action. However, other non-hormone-related mechanisms have also been suggested including antimetastatic and anti-angiogenic....

Anticarcinogenic Activity Of Vitamin A Retinoids And Rexinoids

Vitamin A deficiency has been known as a risk factor for various cancers, such as stomach cancer. Thus, vitamin A has been evaluated as a cancer-suppressing agent. However, it has been found that long-term administration of vitamin A is practically difficult due to its hepatic toxicity. In addition, less toxic vitamin A analogs, retinoids (fenretinide, E5166, Am88, KNK41, and others) and rexinoids (LGD1069, LG100268, and others), have been developed and applied for clinical trials to suppress...

In Vitro Studies

Inhibition of cell growth and modulation of the cell cycle have been reported for allyl ITC (AITC) (10 M), benzyl ITC (BITC) (5 M), and PEITC (2.5 M) in HeLa cells,20 and similar effects have been reported for SF (15 M) in HT-29 cells. Similar results have been reported in other cell lines including human leukemia HL60 and prostate cancer cell lines LNCaP and DU-145 (reviewed by Reference 21). A comprehensive study of the effect of ITCs on the growth of different cancer cells reported that...

Exogenous Sphingolipids To Prevent Cancer In Vivo

The amphiphilic nature of sphingolipid metabolites and their inherent toxicity makes their site-directed administration in vivo a challenge. However, topical, intraperitoneal, and intravenous injections and oral administration of complex sphingolipids and sphingolipid metabolites have been reported. Sencar mice were treated with dimethylbenz- a -anthracene to induce skin cancer. Topical application of sphingosine, methylsphingosine, and N-acetylsphingosine did not inhibit the development of...

Dietary Components That Protect Cancer Specialized Lipids

Chapter 23 Omega-3 Fatty Acids and Cancer Chapter 24 Conjugated Linoleic Acid and Chapter 25 Sphingolipids as Chemopreventive Chapter 26 Obesity as a Cancer Risk Factor Yang Mao, Sai Yi Pan, and Anne-Marie Ugnat Chapter 27 Obesity as a Cancer Risk Factor Potential Mechanisms of Henry J. Thompson, Weiqin Jiang, and Zongjian Zhu Chapter 28 Alcohol and Cancer Cellular Mechanisms of Action 579 Xiang-Dong Wang and Hiroko Inoue-Fruehauf

Contributors

Department of Exercise and Nutrition Sciences Professions State University of New York at Medicine School of Public Health and Health Professions State University of New York at Toxicology School of Medicine and Biomedical Sciences State University of New York at Department of Molecular Pathology Division of Pathology and Laboratory Medicine M.D. Anderson Cancer Center University of Texas Houston, Texas Department of Cancer Biology M.D. Anderson Cancer Center University of Texas Houston, Texas...