1 / 40

Diet and Colon Cancer Prevention

Explore the role of phytochemicals in preventing colon cancer, stages of carcinogenesis, normal vs. cancerous growth, and chemoprevention strategies. Learn about Quercetin, Flavonoids & Limonoids, and citrus compounds in protecting against colon cancer. Dive into inflammation-induced injury and ways to inhibit chronic inflammation using bioactive compounds. Discover insights and breakthroughs in colon cancer prevention through dietary measures.

guinnm
Download Presentation

Diet and Colon Cancer Prevention

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Diet and Colon Cancer Prevention Nancy D. Turner Nutrition & Food Science Department Faculty of Toxicology Faculty of Genetics Vegetable and Fruit Improvement Center Texas A&M University College Station, TX 77843-2253

  2. Overview of Talk • Quick review of colon cancer • Evidence from our lab • Discussion of potentials/pitfalls in use of phytochemicals • Summary

  3. What is Carcinogenesis • Multistep process • Cellular • Molecular • Typically takes many years to develop • Colon cancer can take up to 40 years

  4. Stages of Carcinogenesis • Initiation • Exposure to carcinogenic agents • Changes at the DNA level - selective growth advantage • Promotion • Expansion of initiated cells • Progression • Tumors • Metastasis

  5. Normal Growth and Function • Cell number determined by • Proliferation • Apoptosis • Cell phenotype determined by • Differentiation

  6. Apoptosis Differentiation Proliferation Normal Colon Architecture Goblet cells Epithelial cells

  7. Cancerous Growth • Loss of cell cycle controls • Increased proliferation • Decreased apoptosis • Results from • Genetic changes - mutations/deletions • Epigenetic changes - altered gene expression

  8. Cartoon of Cancer Development Proliferation Apoptosis

  9. Genetic Changes • DNA is damaged by exogenous and endogenous: • Reactive oxygen species • Reactive nitrogen species • Alkylating agents • Lipid peroxidation products

  10. Exogenous vs Endogenous • Exogenous sources of oxidants and carcinogens are found in the diet • Component of food • Result of food processing/cooking • Endogenous sources derived from metabolism • Conversion of pro-carcinogens to ultimate carcinogen • Reactive oxygen species generation

  11. Chemoprevention Opportunities • Reduce formation/uptake of carcinogens • Modification of carcinogen metabolism • Scavenge activated carcinogens • Inhibit DNA adduct formation • Antioxidant activity • Cell cycle activity regulation • Normalize cellular signal transduction

  12. Epidemiological Results • Cancer prevalence is higher in cultures where intake of plant-foods is low • Cancer incidence increases as people migrate from low to high incidence rate environments • More of an effect of environment (e.g., diet) than genetic predisposition

  13. Questions on Colon Carcinogenesis • Chemicals that promote colon cancer are derived from….? • Cancer growth differs from normal growth in what ways? • What are the stages of carcinogenesis and what characterizes the events of that stage?

  14. So What Is in the Diet that Can Protect Us from Colon Cancer?

  15. Quercetin • Quercetin is present in many plant-based foods • Level depends on food source • High plant food diets would provide a reasonable mass of the compound

  16. Quercetin Inhibits Colon Cancer • We demonstrated • Reduction in early colon cancer lesions • Proliferation and apoptosis effects • Lower expression of COX-1, COX-2 Warren et al., 2009; J. Nutrition 139:101

  17. Quercetin Conclusions • Suppresses development of early lesions • Beneficially affects proliferation and apoptosis to return cell numbers to normal levels • Has a small impact on pro-inflammatory mediators

  18. Flavonoids and Limonoids • Citrus contains many different compounds with potential • Evaluated relative protection in 5 diets • Basal • Rio Red grapefruit pulp powder (GFPP, ~1.5/day) • Irradiated Rio Red grapefruit pulp powder (IGFPP) • Isolated Naringin (same level in GFPP) • Isolated Limonin (~10-15 times higher than GFPP, but same level as Naringin)

  19. Early Lesions HMACF Number (% of Basal) P = 0.01 a b b b b All diets reduce formation of these early lesions. Vanamala et al., 2006; Carcinogenesis 27:1257

  20. Proliferative Index Proliferative Index (% of Basal) a P = 0.02 b b b b All diets reduce proliferation with the maximum reduction occurring with the GFPP and limonin diets.

  21. Apoptotic Index Apoptotic Index (% of Basal) c P = 0.02 c b b a The GFPP and limonin diets caused the greatest level of apoptosis

  22. Mechanisms? • Colon cancer is promoted by repeated bouts of inflammation. • Reducing proinflammatory proteins may be protective

  23. Cyclooxygenase - 2 COX-2 Protein Level P < 0.032 a a ab b b COX-2 levels were lowest in rats consuming the GFPP and limonin diets.

  24. What About Other Citrus Compounds • Not all compounds perform equally • Naringenin and Apigenin reduce early lesions • Naringenin reduced proliferation • Naringenin and Apigenin increased apoptosis Leonardi et al., 2010; Experimental Biology & Medicine 235:710

  25. Conclusions for Citrus Flavonoids/Limonoids • Grapefruit and some bioactives reduce colon carcinogenesis • Not all citrus compounds have equal protective ability • Irradiation may negatively affect the chemoprotection provided by grapefruit.

  26. Inflammation • Inflammation promotes colon cancer • Can bioactive compounds inhibit chronic inflammation and injury • Stonefruits • Bran from grains

  27. Inflammation-Induced Injury

  28. Activation of NF-kB

  29. Intestinal Microbiota and IBD • Intestinal bacterial populations (dysbiosis) are tied to development and severity of colitis • Recurrent colitis is a promoter of colon cancer

  30. Colon Microbial Differences • Distinct diet patterns • Brans contain • Anthocyanidins (black) • Condensed tannins (sumac) • Both (high tannin) Cellulose Black Sumac High Tannin Ritchie, Azcarate-Peril, and Turner, In Preparation

  31. Inflammation and Injury Induction Pectin • Black and Sumac sorghum reduced activation of an inflammatory mediator (NF-kB) and resulting injury scores High-Tannin Black Sumac Cellulose Black p=0.01, R2=0.98 Ritchie et al. (unpublished data)

  32. Inflammation Conclusions • During chronic inflammation, injury and inflammation induction are dependent on fiber type • Activation of NF-kB (inflammation regulator) is lowest in rats consuming chlorogenic acid or brans from black or sumac sorghums • Diet has a major impact on microbial populations

  33. Interactions Between Substances • Studying a molecule in isolation ignores potential interactions with other diet components. • One molecule may affect absorption/ availability of another (ß-carotene reduces absorption of other carotenoids) • Compounds may oppose or enhance effects of other compounds

  34. Prevailing Wisdom • Insoluble fiber more protective • Fish oil (omega 3 fatty acid source) would be protective • Hypothesis: • Combination of fish oil and cellulose would reduce tumor incidence

  35. Fat and Fiber in Colon Cancer Rats with Colon Tumors, % a a,b a,b b Chang et al., 1997; Carcinogenesis 18:721

  36. Human Studies Suggest Caution • In both the ATBC and CARET trial - ß-carotene promoted lung cancer • Dietary recommendations, or “treatments”, need to be tailored for the individual, not the population • Recommendations for someone without the disease or in the early stages may differ from those for someone with cancer • Vitamin E and prostate cancer trial (SELECT) was also stopped because of enhanced cancer rates

  37. Supplement vs Functional Food • Supplements • Bolus of compound • Usually in a purified form • Functional food • Smaller amount of compound • Slows delivery • Competes/complements other molecules present in food

  38. Is it Always a Chemoprotectant? • Although a molecule may protect against a certain type of cancer, it is not always beneficial to all systems • Need to evaluate multiple mechanisms • Need to study a variety of tissues/diseases • Will require more data • How does processing affect responses

  39. Summary • Many potential chemoprotectants • More work is needed to identify individuals in populations that will benefit • Must be aware of potential interactions • Functional foods probably more desirable than nutraceutical supplements

  40. Bioactive Questions • Are all bioactive compounds effective at preventing colon cancer? • What are the possible mechanisms of chemoprotection conferred by bioactive compounds? • What are the pros and cons of using a supplement vs getting compounds via the food?

More Related