Comparative Mechanisms of Cancer Chemoprevention

Summary

Principal Investigator: Roderick H Dashwood
Abstract: DESCRIPTION (provided by applicant): The NIH Roadmap stipulates that epigenetics is a research priority. Unlike genetic changes associated with cancer, epigenetic changes are potentially modifiable, and dietary factors have been shown to "de-repress" epigenetically-silenced genes in cancer cells, triggering cell cycle arrest and apoptosis. The overall long-term objectives of this P01 are to better understand the mechanisms by which beneficial epigenetic changes can be brought about by dietary agents, to identify and characterize epigenetic biomarkers that can be applied in the clinical setting, and to evaluate those biomarkers in preclinical and translational studies. With three well-integrated Projects and a complementary Epigenetic/Translational Biomarkers Core, this competing continuation addresses the application (and possible risks) of dietary indoles and isothiocyanates for cancer intervention, through comparative mechanism, biomarker, and preclinical models (lymphoma, prostate, colon, lung cancer), leading to translational studies of epigenetic biomarkers in human volunteers. The CENTRAL HYPOTHESIS is that sulforaphane (SFN) and indole-3-carbinol (ISC), and the cruciferous vegetables from which they derive, are effective chemopreventive agents because, in addition to their blocking activities during the initiation phase, they alter the pattern of histone modifications (acetylation, methylation, phosphorylation) and histone deacetylase (HDAC) activity in cancer cells, as well as DNA promoter methylation status, thereby de-repressing epigenetically silenced genes that regulate the cell cycle and apoptosis. E. Ho will investigate "Chemoprevention of prostate cancer, HDAC inhibition, and DNA methylation" (Project 1), D.E. Williams will study "Transplacental chemoprevention of lung tumors and lymphomas" (Project 2), and R.H. Dashwood will examine "Chemoprevention of colon cancer, HDAC inhibition, and histone status" (Project 3). The overall significance of the work is that it seeks to provide new epigenetic insights into the prevention and treatment of colon, prostate, and lung cancer, as well as lymphoma, which are listed consistently among the top causes of cancer-related deaths in the US. This application is innovative and timely in bridging basic mechanisms, preclinical models, and human studies of epigenetics and diet.
Funding Period: 2001-04-01 - 2015-04-30
more information: NIH RePORT

Top Publications

  1. pmc Effects of sulforaphane and 3,3'-diindolylmethane on genome-wide promoter methylation in normal prostate epithelial cells and prostate cancer cells
    Carmen P Wong
    School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, United States of America Linus Pauling Institute, Oregon State University, Corvallis, Oregon, United States of America
    PLoS ONE 9:e86787. 2014
  2. pmc Metabolism and tissue distribution of sulforaphane in Nrf2 knockout and wild-type mice
    John D Clarke
    Molecular and Cellular Biology Program, Oregon State University, Corvallis, Oregon 97331, USA
    Pharm Res 28:3171-9. 2011
  3. pmc Histone deacetylase turnover and recovery in sulforaphane-treated colon cancer cells: competing actions of 14-3-3 and Pin1 in HDAC3/SMRT corepressor complex dissociation/reassembly
    Praveen Rajendran
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 6512, USA
    Mol Cancer 10:68. 2011
  4. pmc Metabolism as a key to histone deacetylase inhibition
    Praveen Rajendran
    Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
    Crit Rev Biochem Mol Biol 46:181-99. 2011
  5. pmc Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells
    John D Clarke
    Molecular and Cellular Biology Program, Oregon State University, Corvallis, OR 97331, USA
    Mol Nutr Food Res 55:999-1009. 2011
  6. pmc Endothelins and their receptors in cancer: identification of therapeutic targets
    Rong Wang
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 6512, USA
    Pharmacol Res 63:519-24. 2011
  7. pmc NADPH oxidase overexpression in human colon cancers and rat colon tumors induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)
    Rong Wang
    Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331, USA
    Int J Cancer 128:2581-90. 2011
  8. pmc Tea catechins as inhibitors of receptor tyrosine kinases: mechanistic insights and human relevance
    Christine A Larsen
    Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
    Pharmacol Res 62:457-64. 2010
  9. pmc (-)-Epigallocatechin-3-gallate inhibits Met signaling, proliferation, and invasiveness in human colon cancer cells
    Christine A Larsen
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 6512, USA
    Arch Biochem Biophys 501:52-7. 2010
  10. pmc Targeting drug-metabolizing enzymes for effective chemoprevention and chemotherapy
    Hollie I Swanson
    Department of Molecular and Biomedical Pharmacology, University of Kentucky College of Medicine, Lexington, USA
    Drug Metab Dispos 38:539-44. 2010

Detail Information

Publications76

  1. pmc Effects of sulforaphane and 3,3'-diindolylmethane on genome-wide promoter methylation in normal prostate epithelial cells and prostate cancer cells
    Carmen P Wong
    School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, United States of America Linus Pauling Institute, Oregon State University, Corvallis, Oregon, United States of America
    PLoS ONE 9:e86787. 2014
    ..Results from our study may provide new insights into the epigenetic mechanisms by which SFN and DIM exert their cancer chemopreventive effects. ..
  2. pmc Metabolism and tissue distribution of sulforaphane in Nrf2 knockout and wild-type mice
    John D Clarke
    Molecular and Cellular Biology Program, Oregon State University, Corvallis, Oregon 97331, USA
    Pharm Res 28:3171-9. 2011
    ..To determine the metabolism and tissue distribution of the dietary chemoprotective agent sulforaphane following oral administration to wild-type and Nrf2 knockout (Nrf2(-/-)) mice...
  3. pmc Histone deacetylase turnover and recovery in sulforaphane-treated colon cancer cells: competing actions of 14-3-3 and Pin1 in HDAC3/SMRT corepressor complex dissociation/reassembly
    Praveen Rajendran
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 6512, USA
    Mol Cancer 10:68. 2011
    ..Here, we examined the time-course and reversibility of SFN-induced HDAC changes in human colon cancer cells...
  4. pmc Metabolism as a key to histone deacetylase inhibition
    Praveen Rajendran
    Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
    Crit Rev Biochem Mol Biol 46:181-99. 2011
    ..g. pyruvate), the yin-yang of HDAC inhibition versus HDAC activation, and the screening assays that might be most appropriate for discovery of novel HDAC inhibitors in the future...
  5. pmc Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells
    John D Clarke
    Molecular and Cellular Biology Program, Oregon State University, Corvallis, OR 97331, USA
    Mol Nutr Food Res 55:999-1009. 2011
    ..The ability of a chemopreventive agent to specifically cause cytotoxicity in cancer and not normal cells is an important factor in determining its safety and clinical relevance...
  6. pmc Endothelins and their receptors in cancer: identification of therapeutic targets
    Rong Wang
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 6512, USA
    Pharmacol Res 63:519-24. 2011
    ..The endothelin axis continues to be an attractive avenue of scientific endeavor, both in the cancer arena and in other important health-related disciplines...
  7. pmc NADPH oxidase overexpression in human colon cancers and rat colon tumors induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)
    Rong Wang
    Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331, USA
    Int J Cancer 128:2581-90. 2011
    ..Collectively, the findings from this investigation and others suggest that further work is warranted on the role of Nox/Duox family members and NFκB in colon cancer development...
  8. pmc Tea catechins as inhibitors of receptor tyrosine kinases: mechanistic insights and human relevance
    Christine A Larsen
    Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
    Pharmacol Res 62:457-64. 2010
    ..The findings are discussed in the context of ongoing clinical trials with RTK inhibitors, and the possibility for drug/nutrient interactions enhancing therapeutic efficacy...
  9. pmc (-)-Epigallocatechin-3-gallate inhibits Met signaling, proliferation, and invasiveness in human colon cancer cells
    Christine A Larsen
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 6512, USA
    Arch Biochem Biophys 501:52-7. 2010
    ..These findings are discussed in the context of the pleiotropic effects of tea catechins, their tissue metabolite levels, and the potential to inhibit colon cancer metastasis and invasion...
  10. pmc Targeting drug-metabolizing enzymes for effective chemoprevention and chemotherapy
    Hollie I Swanson
    Department of Molecular and Biomedical Pharmacology, University of Kentucky College of Medicine, Lexington, USA
    Drug Metab Dispos 38:539-44. 2010
    ..In addition to highlighting recent successes in these areas, limitations and areas that should be targeted for further investigation are discussed...
  11. ncbi Effects of chlorophyll and chlorophyllin on low-dose aflatoxin B(1) pharmacokinetics in human volunteers
    Carole Jubert
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA
    Cancer Prev Res (Phila) 2:1015-22. 2009
    ..These initial results provide AFB(1) pharmacokinetic parameters previously unavailable for humans, and suggest that Chla or CHL co-consumption may limit the bioavailability of ingested aflatoxin in humans, as they do in animal models...
  12. pmc Tea catechins inhibit hepatocyte growth factor receptor (MET kinase) activity in human colon cancer cells: kinetic and molecular docking studies
    Christine A Larsen
    Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331, USA
    J Med Chem 52:6543-5. 2009
    ..Here we report on the ability of tea catechins to suppress MET activation in human colon cancer cells and propose a mechanism by which they might compete for the kinase domain of the MET protein...
  13. pmc Dietary sulforaphane, a histone deacetylase inhibitor for cancer prevention
    Emily Ho
    Department of Nutrition and Exercise Sciences, Oregon State University, Corvallis OR 97331, USA
    J Nutr 139:2393-6. 2009
    ..These studies also will provide a strong scientific foundation for future large-scale human clinical intervention studies...
  14. pmc Suppression of Met activation in human colon cancer cells treated with (-)-epigallocatechin-3-gallate: minor role of hydrogen peroxide
    Christine A Larsen
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 6512, USA
    Biochem Biophys Res Commun 389:527-30. 2009
    ..We conclude that EGCG might be a beneficial therapeutic agent in the colon, inhibiting Met signaling and helping to attenuate tumor spread/metastasis, independent of H(2)O(2)-related mechanisms...
  15. pmc E2F4 and ribonucleotide reductase mediate S-phase arrest in colon cancer cells treated with chlorophyllin
    Korakod Chimploy
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 6512, USA
    Int J Cancer 125:2086-94. 2009
    ..We conclude that by inhibiting R1, R2, and p53R2, CHL has the potential to be effective in the clinical setting, when used alone or in combination with currently available cancer therapeutic agents...
  16. pmc Alpha-keto acid metabolites of naturally occurring organoselenium compounds as inhibitors of histone deacetylase in human prostate cancer cells
    Jeong In Lee
    Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA
    Cancer Prev Res (Phila) 2:683-93. 2009
    ..These findings provide a potential new paradigm by which naturally occurring organoselenium might prevent the progression of human prostate cancer...
  17. pmc MicroRNAs, diet, and cancer: new mechanistic insights on the epigenetic actions of phytochemicals
    Mansi A Parasramka
    Department of Environmental and Molecular Toxicology, and Linus Pauling Institute, Oregon State University, Corvallis, Oregon, USA
    Mol Carcinog 51:213-30. 2012
    ..We also discuss the mechanisms by which dietary factors regulate miRNA expression, in the context of chemoprevention versus therapy...
  18. pmc Capsaicin represses transcriptional activity of β-catenin in human colorectal cancer cells
    Seong Ho Lee
    Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 4542, USA
    J Nutr Biochem 23:646-55. 2012
    ..This study identifies a role for the β-catenin/TCF-dependent pathway that potentially contributes to the anticancer activity of capsaicin in human colorectal cancer cells...
  19. pmc The epigenome as a potential mediator of cancer and disease prevention in prenatal development
    Pushpinder Kaur
    Linus Pauling Science Center, Oregon State University, Corvallis, Oregon 97331, USA
    Nutr Rev 71:441-57. 2013
    ....
  20. pmc Phytochemicals from cruciferous vegetables, epigenetics, and prostate cancer prevention
    Gregory W Watson
    Molecular and Cellular Biology, Oregon State University, Corvallis, Oregon, 97331, USA
    AAPS J 15:951-61. 2013
    ....
  21. pmc HDAC turnover, CtIP acetylation and dysregulated DNA damage signaling in colon cancer cells treated with sulforaphane and related dietary isothiocyanates
    Praveen Rajendran
    Linus Pauling Institute Oregon State University Corvallis, OR USA
    Epigenetics 8:612-23. 2013
    ..Future studies will address the mechanistic basis for dietary ITCs preferentially exploiting HDAC turnover mechanisms and faulty DNA repair pathways in colon cancer cells vs. normal cells...
  22. pmc Differential modulation of dibenzo[def,p]chrysene transplacental carcinogenesis: maternal diets rich in indole-3-carbinol versus sulforaphane
    Lyndsey E Shorey
    Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 USA
    Toxicol Appl Pharmacol 270:60-9. 2013
    ..These findings provide justification for further study of the safety and bioactivity of cruciferous vegetable phytochemicals at supplemental concentrations during the perinatal period...
  23. pmc The role of estrogen receptor β in transplacental cancer prevention by indole-3-carbinol
    Abby D Benninghoff
    Department of Animal, Dairy and Veterinary Sciences, Utah State University, 4815 Old Main Hill, Logan, UT 84322, USA
    Cancer Prev Res (Phila) 6:339-48. 2013
    ..These findings suggest that I3C may act via ERβ to prevent or suppress DBC-initiated transplacental carcinogenesis but that the involvement of this receptor seems to differ depending on the cancer type and gender of the offspring...
  24. pmc Epigenetic inactivation of endothelin-2 and endothelin-3 in colon cancer
    Rong Wang
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA
    Int J Cancer 132:1004-12. 2013
    ....
  25. pmc 3,3'-Diindolylmethane, but not indole-3-carbinol, inhibits histone deacetylase activity in prostate cancer cells
    Laura M Beaver
    Linus Pauling Institute, Oregon State University, 307 Linus Pauling Science Center, Corvallis, OR 97331, USA
    Toxicol Appl Pharmacol 263:345-51. 2012
    ..The ability of DIM to target aberrant epigenetic patterns, in addition to its effects on detoxification of carcinogens, may make it an effective chemopreventive agent by targeting multiple stages of prostate carcinogenesis...
  26. pmc MicroRNA profiling of carcinogen-induced rat colon tumors and the influence of dietary spinach
    Mansi A Parasramka
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA
    Mol Nutr Food Res 56:1259-69. 2012
    ..A systems biology approach was used to examine, for the first time, miRNAs altered in rat colon tumors induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine carcinogen from cooked meat...
  27. pmc 3,3'-Diindolylmethane induces G1 arrest and apoptosis in human acute T-cell lymphoblastic leukemia cells
    Lyndsey E Shorey
    Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon, United States of America
    PLoS ONE 7:e34975. 2012
    ..Taken together, our results demonstrate a potential for therapeutic application of DIM in T-ALL...
  28. pmc SEL1L, an UPR response protein, a potential marker of colonic cell transformation
    Hassan Ashktorab
    Department of Medicine and Cancer Center, Howard University College of Medicine, 2041 Georgia Avenue, NW, Washington, DC 20060, USA
    Dig Dis Sci 57:905-12. 2012
    ..This gene and associated miRNAs have been indicated as predictive and prognostic markers of pancreatic cancer...
  29. pmc Dietary factors and epigenetic regulation for prostate cancer prevention
    Emily Ho
    Linus Pauling Institute, Department of Nutrition and Exercise Sciences, Oregon State University, Corvallis, OR, USA
    Adv Nutr 2:497-510. 2011
    ..In particular, we focus on epigenetic dysregulation and the impact of specific nutrients and food components on DNA methylation and histone modifications that can alter gene expression and influence prostate cancer progression...
  30. pmc Promoter de-methylation of cyclin D2 by sulforaphane in prostate cancer cells
    Anna Hsu
    School of Biological and Population Health Sciences, 103 Milam Hall, Oregon State University, Corvallis, OR 97331, USA
    Clin Epigenetics 3:3. 2011
    ..Our results demonstrated the ability of SFN to epigenetically modulate cyclin D2 expression, and provide novel insights into the mechanisms by which SFN may regulate gene expression as a prostate cancer chemopreventive agent...
  31. pmc Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells
    Praveen Rajendran
    Cancer Chemoprotection Program, Linus Pauling Institute, 307 Linus Pauling Science Center, Oregon State University, Corvallis OR 97331, USA
    Clin Epigenetics 3:4. 2011
    ....
  32. pmc Transplacental carcinogenesis with dibenzo[def,p]chrysene (DBC): timing of maternal exposures determines target tissue response in offspring
    Lyndsey E Shorey
    Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA
    Cancer Lett 317:49-55. 2012
    ..This study highlights the importance of developmental stage in susceptibility to environmental carcinogens...
  33. pmc Cancer chemoprevention by dietary chlorophylls: a 12,000-animal dose-dose matrix biomarker and tumor study
    Tammie J McQuistan
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA
    Food Chem Toxicol 50:341-52. 2012
    ..This finding questions the human relevance of chemoprevention studies carried out at high carcinogen doses that are not proven to lie within a linear, or at least monotonic, endpoint dose-response range...
  34. pmc Comparison of isothiocyanate metabolite levels and histone deacetylase activity in human subjects consuming broccoli sprouts or broccoli supplement
    John D Clarke
    Department of Nutrition and Exercise Sciences, Oregon State University, Corvallis, Oregon 97331, United States
    J Agric Food Chem 59:10955-63. 2011
    ..Fresh broccoli sprouts differ from broccoli supplements in regards to excretion of isothiocyanates and bioactivity in human subjects...
  35. pmc Bioavailability and inter-conversion of sulforaphane and erucin in human subjects consuming broccoli sprouts or broccoli supplement in a cross-over study design
    John D Clarke
    Department of Nutrition and Exercise Sciences, Oregon State University, Corvallis, OR 97331, USA
    Pharmacol Res 64:456-63. 2011
    ..This has implications for people who consume the recommended serving size (1 pill) of a broccoli supplement and believe they are getting equivalent doses of isothiocyanates...
  36. pmc Alpha-keto acid metabolites of organoselenium compounds inhibit histone deacetylase activity in human colon cancer cells
    Hui Nian
    Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA
    Carcinogenesis 30:1416-23. 2009
    ....
  37. pmc Activator protein 2alpha suppresses intestinal tumorigenesis in the Apc(min) mouse
    Qingjie Li
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 6512, USA
    Cancer Lett 283:36-42. 2009
    ....
  38. ncbi Natural chlorophyll inhibits aflatoxin B1-induced multi-organ carcinogenesis in the rat
    Michael T Simonich
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA
    Carcinogenesis 28:1294-302. 2007
    ..0026) and 75% (P = 0.0004), respectively. These results show Chl and CHL provide potent chemoprotection against early biochemical and late pathophysiological biomarkers of AFB(1) carcinogenesis in the rat liver and colon...
  39. ncbi Gene expression analysis during tumor enhancement by the dietary phytochemical, 3,3'-diindolylmethane, in rainbow trout
    Susan C Tilton
    Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA
    Carcinogenesis 28:1589-98. 2007
    ..They confirm the importance of estrogenic signaling in the mechanism of promotion by dietary indoles in trout liver and indicate a possible dual effect that enhances tumor incidence and decreases potential for metastasis...
  40. pmc Sulforaphane retards the growth of human PC-3 xenografts and inhibits HDAC activity in human subjects
    Melinda C Myzak
    Linus Pauling Institute, Molecular and Cellular Biology Program, Oregon State University, Corvallis, Oregon 97331, USA
    Exp Biol Med (Maywood) 232:227-34. 2007
    ..Moreover, the data suggest that HDAC activity in PBMC may be used as a biomarker for assessing exposure to novel dietary HDAC inhibitors in human subjects...
  41. ncbi Frontiers in polyphenols and cancer prevention
    Roderick H Dashwood
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA
    J Nutr 137:267S-269S. 2007
  42. ncbi Isolation of chlorophylls a and b from spinach by counter-current chromatography
    Carole Jubert
    Linus Pauling Institute, Oregon State University, 435 Weniger Hall, Corvallis, OR 97331, USA
    J Chromatogr A 1140:95-100. 2007
    ..Purity was estimated to be >95% (100% by HPLC). Typical yields from 30g of freeze-dried spinach were 300mg of chlorophyll a and 100mg of chlorophyll b...
  43. pmc Antioxidant and antigenotoxic activities of Angelica keiskei, Oenanthe javanica and Brassica oleracea in the Salmonella mutagenicity assay and in HCT116 human colon cancer cells
    Daejoong Kwon
    Department of Foods and Nutrition, Yonsei University, Seoul, Korea 120 749
    Biofactors 26:231-44. 2006
    ..keiskei, O. javanica, and B. oleracea, through mechanisms that include inhibition of carcinogen activation and scavenging of reactive oxygen species...
  44. ncbi Xenobiotic metabolism relevance to cancer
    Roderick H Dashwood
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 6512, USA
    J Nutr 136:2681S-2S. 2006
  45. pmc Tumors from rats given 1,2-dimethylhydrazine plus chlorophyllin or indole-3-carbinol contain transcriptional changes in beta-catenin that are independent of beta-catenin mutation status
    Rong Wang
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA
    Mutat Res 601:11-8. 2006
    ..Thus, further studies are warranted on the mechanisms that upregulate beta-catenin at the transcriptional level in human and rodent colon cancers...
  46. ncbi Indole-3-carbinol in the maternal diet provides chemoprotection for the fetus against transplacental carcinogenesis by the polycyclic aromatic hydrocarbon dibenzo[a,l]pyrene
    Zhen Yu
    Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 7301, USA
    Carcinogenesis 27:2116-23. 2006
    ..Addition of chemoprotective agents to the maternal diet during pregnancy and nursing may be an effective new approach in reducing the incidence of cancers in children and young adults...
  47. pmc Dietary agents as histone deacetylase inhibitors
    Melinda C Myzak
    Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331 6512, USA
    Mol Carcinog 45:443-6. 2006
    ....
  48. ncbi Histone deacetylases as targets for dietary cancer preventive agents: lessons learned with butyrate, diallyl disulfide, and sulforaphane
    Melinda C Myzak
    Linus Pauling Institute, Weniger 503, Oregon State University, Corvallis, 97331 6512, USA
    Curr Drug Targets 7:443-52. 2006
    ..This review discusses the role of aberrant histone acetylation in tumorigenesis and describes the potential for cancer chemoprevention and therapy with a particular emphasis on dietary HDAC inhibitors...
  49. pmc Chemoprotection by sulforaphane: keep one eye beyond Keap1
    Melinda C Myzak
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA
    Cancer Lett 233:208-18. 2006
    ..The present review discusses the more widely established chemoprotective mechanisms of SFN, but makes the case for additional work on mechanisms that might be of importance during later stages of carcinogenesis, beyond Keap1...
  50. ncbi Plant polyphenols and multidrug resistance: effects of dietary flavonoids on drug transporters in Caco-2 and MDCKII-MDR1 cell transport models
    R Rodriguez-Proteau
    Department of Pharmaceutical Sciences, Oregon State University, Corvallis, 97331 3507, USA
    Xenobiotica 36:41-58. 2006
    ..The transport data suggests that xanthohumol effects transport of CSA in a manner that is distinct from the digoxin efflux pathway and suggests that intestinal transport of these MDR1 substrates is more complex than previously reported...
  51. ncbi In utero exposure of mice to dibenzo[a,l]pyrene produces lymphoma in the offspring: role of the aryl hydrocarbon receptor
    Zhen Yu
    Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 7301, USA
    Cancer Res 66:755-62. 2006
    ....
  52. pmc Sulforaphane inhibits histone deacetylase in vivo and suppresses tumorigenesis in Apc-minus mice
    Melinda C Myzak
    Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331 6512, USA
    FASEB J 20:506-8. 2006
    ....
  53. pmc Sulforaphane inhibits histone deacetylase activity in BPH-1, LnCaP and PC-3 prostate epithelial cells
    Melinda C Myzak
    Linus Pauling Institute, Molecular and Cellular Biology Program, Department of Nutrition and Exercise Sciences, Oregon State University, Corvallis, OR 97331, USA
    Carcinogenesis 27:811-9. 2006
    ....
  54. pmc Dietary HDAC inhibitors: time to rethink weak ligands in cancer chemoprevention?
    Roderick H Dashwood
    Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 6512, USA
    Carcinogenesis 27:344-9. 2006
    ....
  55. pmc Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis
    Jane V Higdon
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 6512, USA
    Pharmacol Res 55:224-36. 2007
    ....
  56. pmc Bcl-2 overexpression in PhIP-induced colon tumors: cloning of the rat Bcl-2 promoter and characterization of a pathway involving beta-catenin, c-Myc and E2F1
    Q Li
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 6512, USA
    Oncogene 26:6194-202. 2007
    ..These findings suggest an indirect pathway for Bcl-2 over-expression in PhIP-induced colon tumors involving beta-catenin, c-Myc and E2F1...
  57. pmc Modulation of histone deacetylase activity by dietary isothiocyanates and allyl sulfides: studies with sulforaphane and garlic organosulfur compounds
    Hui Nian
    Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331 6512, USA
    Environ Mol Mutagen 50:213-21. 2009
    ..Collectively, the results from these studies, and others reviewed herein, provide new insights into the relationships between reversible histone modifications, diet, and cancer chemoprevention...
  58. pmc Fetal mouse Cyp1b1 and transplacental carcinogenesis from maternal exposure to dibenzo(a,l)pyrene
    David J Castro
    Department of Environmental and Molecular Toxicology, Oregon State University, ALS 1007, Corvallis, OR 97331 7301, USA
    Cancer Prev Res (Phila) 1:128-34. 2008
    ..0). These data confirm that cyp1b1 bioactivation of DBP occurs in fetal target tissues, following transplacental exposure, with the thymus and lung as primary and secondary targets, respectively...
  59. pmc Identifying efficacious approaches to chemoprevention with chlorophyllin, purified chlorophylls and freeze-dried spinach in a mouse model of transplacental carcinogenesis
    David J Castro
    Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 7301, USA
    Carcinogenesis 30:315-20. 2009
    ..005). This is the first demonstration that CHL can provide potent chemoprotection in a transplacental carcinogenesis model and support a mechanism involving complex-mediated reduction of carcinogen uptake...
  60. ncbi Effects of dietary flavonoids on the transport of cimetidine via P-glycoprotein and cationic transporters in Caco-2 and LLC-PK1 cell models
    J S Taur
    Drug Safety and Disposition, Eisai Research Institute, Andover, MA, USA
    Xenobiotica 38:1536-50. 2008
    ..These results suggest that flavonoids may have potential to alter the disposition profile of cimetidine and possibly other therapeutics that are mediated by P-gp and/or cation transport systems...
  61. pmc Lymphoma and lung cancer in offspring born to pregnant mice dosed with dibenzo[a,l]pyrene: the importance of in utero vs. lactational exposure
    David J Castro
    Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 7301, USA
    Toxicol Appl Pharmacol 233:454-8. 2008
    ..Our results demonstrate that short exposure to DBP during late gestation presents a greater risk to offspring than exposure to this very hydrophobic PAH following 3 weeks of nursing...
  62. pmc Chemoprevention of dibenzo[a,l]pyrene transplacental carcinogenesis in mice born to mothers administered green tea: primary role of caffeine
    David J Castro
    Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA
    Carcinogenesis 29:1581-6. 2008
    ..This is the first demonstration that maternal ingestion of green tea, during pregnancy and nursing, provides protection against transplacental carcinogenesis...
  63. pmc Allyl mercaptan, a garlic-derived organosulfur compound, inhibits histone deacetylase and enhances Sp3 binding on the P21WAF1 promoter
    Hui Nian
    Linus Pauling Institute, Oregon State University, 571 Weniger Hall, Corvallis, OR 97331 6512, USA
    Carcinogenesis 29:1816-24. 2008
    ..The results are discussed in the context of other anticarcinogenic mechanisms ascribed to garlic organosulfur compounds and the metabolic conversion of such compounds to potential HDAC inhibitors in situ...
  64. pmc beta-catenin is strongly elevated in rat colonic epithelium following short-term intermittent treatment with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and a high-fat diet
    Rong Wang
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 6512, USA
    Cancer Sci 99:1754-9. 2008
    ..Thus, during the early stages of colon carcinogenesis, alternating exposure to heterocyclic amines and a high-fat diet might facilitate molecular changes resulting in dysregulated beta-catenin and c-myc expression...
  65. pmc Dietary manipulation of histone structure and function
    Barbara Delage
    Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331 6512, USA
    Annu Rev Nutr 28:347-66. 2008
    ....
  66. pmc Multi-targeted prevention of cancer by sulforaphane
    John D Clarke
    Department of Nutrition and Exercise Sciences, 117 Milam Hall, Oregon State University, Corvallis, OR 97331, USA
    Cancer Lett 269:291-304. 2008
    ..The current status of SFN in human clinical trials also is included, with consideration of the chemistry, metabolism, absorption and factors influencing SFN bioavailability...
  67. pmc Protective versus promotional effects of white tea and caffeine on PhIP-induced tumorigenesis and beta-catenin expression in the rat
    Rong Wang
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA
    Carcinogenesis 29:834-9. 2008
    ..These findings are discussed in the context of epidemiological data which do not support an adverse effect of tea and coffee on colon tumor outcome-indeed, some such studies suggest a protective role for caffeinated beverages...
  68. ncbi Ketoconazole and the modulation of multidrug resistance-mediated transport in Caco-2 and MDCKII-MDR1 drug transport models
    Y Fan
    Pharmaceutical Sciences, Oregon State University, Corvallis, OR 97330 3507, USA
    Xenobiotica 38:107-29. 2008
    ..In conclusion, ketoconazole modulates the P(app) of P-glycoprotein substrates by interacting with MDR1 protein. Epigallocatechin-3-gallate and xanthohumol modulate the transport and uptake of ketoconazole...
  69. pmc Low-dose dietary chlorophyll inhibits multi-organ carcinogenesis in the rainbow trout
    Michael T Simonich
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA
    Food Chem Toxicol 46:1014-24. 2008
    ..001). This is the first demonstration that dietary Chl can reduce tumorigenesis in any whole animal model, and that it may do so by a simple, species-independent mechanism...
  70. ncbi Protective effect of dietary tomatine against dibenzo[a,l]pyrene (DBP)-induced liver and stomach tumors in rainbow trout
    Mendel Friedman
    Western Regional Research Center, Agricultural Research Service, U S Department of Agriculture, Albany, CA 94710, USA
    Mol Nutr Food Res 51:1485-91. 2007
    ..Dose-response and chemopreventive mechanisms for tomatine protection remain to be examined. This is the first report on the anticarcinogenic effects of tomatine in vivo...
  71. ncbi Comparison of white tea, green tea, epigallocatechin-3-gallate, and caffeine as inhibitors of PhIP-induced colonic aberrant crypts
    Orianna Carter
    Ohio University Southern, 1804 Liberty Avenue, Ironton, OH 45638, USA
    Nutr Cancer 58:60-5. 2007
    ..5 +/- 0.4 (P > 0.05, not significant). The data imply that white tea, caffeine, and EGCG may be most effective post-initiation, via the inhibition of cell proliferation in the colon and through the suppression of early lesions...
  72. pmc Dietary histone deacetylase inhibitors: from cells to mice to man
    Roderick H Dashwood
    Linus Pauling Institute, Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA
    Semin Cancer Biol 17:363-9. 2007
    ..In a broader context, there is growing interest in dietary HDAC inhibitors and their impact on epigenetic mechanisms affecting other chronic conditions, such as cardiovascular disease, neurodegeneration and aging...
  73. ncbi Toxicogenomic profiling of the hepatic tumor promoters indole-3-carbinol, 17beta-estradiol and beta-naphthoflavone in rainbow trout
    Susan C Tilton
    Department of Environmental and Molecular Toxicology, Marine and Freshwater Biomedical Sciences Center and Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331, USA
    Toxicol Sci 90:61-72. 2006
    ..These data indicate I3C promotes hepatocarcinogenesis through estrogenic mechanisms in trout liver and suggest DIM may be an even more potent hepatic tumor promoter in this model...