题名

Cancer Chemoprevention by Traditional Chinese Herbal Medicine and Dietary Phytochemicals: Targeting Nrf2-Mediated Oxidative Stress/Anti-Inflammatory Responses, Epigenetics, and Cancer Stem Cells

作者

Jong Hun Lee;Limin Shu;Francisco Fuentes;Zheng-Yuan Su;Ah-Ng Tony Kong

关键词

Cancer chemoprevention ; Cancer stem cells ; Epigenetics ; Nrf2 ; Phytochemicals ; Traditional Chinese herbal medicine

期刊名称

Journal of Traditional and Complementary Medicine

卷期/出版年月

3卷1期(2013 / 01 / 01)

页次

69 - 79

内容语文

英文

中文摘要

Excessive oxidative stress induced by reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive metabolites of carcinogens alters cellular homeostasis, leading to genetic/epigenetic changes, genomic instability, neoplastic transformation, and cancer initiation/progression. As a protective mechanism against oxidative stress, antioxidant/detoxifying enzymes reduce these reactive species and protect normal cells from endo-/exogenous oxidative damage. The transcription factor nuclear factor-erythroid 2 p45 (NF-E2)-related factor 2 (Nrf2), a master regulator of the antioxidative stress response, plays a critical role in the expression of many cytoprotective enzymes, including NAD(P)H:quinine oxidoreductase (NQO1), heme oxygenase-1 (HO-1), UDP-glucuronosyltransferase (UGT), and glutathione S-transferase (GST). Recent studies demonstrated that many dietary phytochemicals derived from various vegetables, fruits, spices, and herbal medicines induce Nrf2-mediated antioxidant/detoxifying enzymes, restore aberrant epigenetic alterations, and eliminate cancer stem cells (CSCs). The Nrf2-mediated antioxidant response prevents many age-related diseases, including cancer. Owing to their fundamental contribution to carcinogenesis, epigenetic modifications and CSCs are novel targets of dietary phytochemicals and traditional Chinese herbal medicine (TCHM). In this review, we summarize cancer chemoprevention by dietary phytochemicals, including TCHM, which have great potential as a safer and more effective strategy for preventing cancer.

主题分类 醫藥衛生 > 中醫藥學
参考文献
  1. Ahmad, R,Raina, D,Meyer, C,Kharbanda, S,Kufe, D(2006).Triterpenoid CDDO-Me blocks the NF-kappaB pathway by direct inhibition of IKKbeta on Cys-179.J Biol Chem,281,35764-35769.
  2. Al-Hajj, M,Wicha, MS,Benito-Hernandez, A,Morrison, SJ,Clarke, MF(2003).Prospective identification of tumorigenic breast cancer cells.Proc Natl Acad Sci U S A,100,3983-3988.
  3. Alvero, AB,Chen, R,Fu, HH,Montagna, M,Schwartz, PE,Rutherford, T(2009).Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance.Cell Cycle,8,158-166.
  4. Arasaradnam, RP,Commane, DM,Bradburn, D,Mathers, JC(2008).A review of dietary factors and its influence on DNA methylation in colorectal carcinogenesis.Epigenetics,3,193-198.
  5. Bannister, AJ,Kouzarides, T(2011).Regulation of chromatin by histone modifications.Cell Res,21,381-395.
  6. Bannister, AJ,Zegerman, P,Partridge, JF,Miska, EA,Thomas, JO,Allshire, RC(2001).Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain.Nature,410,120-124.
  7. Barve, A,Khor, TO,Hao, X,Keum, YS,Yang, CS,Reddy, B(2008).Murine prostate cancer inhibition by dietary phytochemicals--curcumin and phenyethylisothiocyanate.Pharm Res,25,2181-2189.
  8. Barve, A,Khor, TO,Nair, S,Reuhl, K,Suh, N,Reddy, B(2009).Gamma-tocopherol-enriched mixed tocopherol diet inhibits prostate carcinogenesis in TRAMP mice.Int J Cancer,124,1693-1699.
  9. Berger, SL(2007).The complex language of chromatin regulation during transcription.Nature,447,407-412.
  10. Bloom, DA,Jaiswal, AK(2003).Phosphorylation of Nrf2 at Ser40 by protein kinase C in response to antioxidants leads to the release of Nrf2 from INrf2, but is not required for Nrf2 stabilization/accumulation in the nucleus and transcriptional activation of antioxidant response element-mediated NAD(P)H:quinone oxidoreductase-1 gene expression.J Biol Chem,278,44675-44682.
  11. Boddupalli, S,Mein, JR,Lakkanna, S,James, DR(2012).Induction of phase 2 antioxidant enzymes by broccoli sulforaphane: Perspectives in maintaining the antioxidant activity of vitamins a, C, and e.Front Genet,3,7.
  12. Bolden, JE,Peart, MJ,Johnstone, RW(2006).Anticancer activities of histone deacetylase inhibitors.Nat Rev Drug Discov,5,769-784.
  13. Bonizzi, G,Karin, M(2004).The two NF-kappaB activation pathways and their role in innate and adaptive immunity.Trends Immunol,25,280-288.
  14. Bonnet, D,Dick, JE(1997).Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell.Nat Med,3,730-737.
  15. Brait, M,Sidransky, D(2011).Cancer epigenetics: Above and beyond.Toxicol Mech Methods,21,275-288.
  16. Cataldi, A(2010).Cell responses to oxidative stressors.Curr Pharm Des,16,1387-1395.
  17. Checker, R,Patwardhan, RS,Sharma, D,Menon, J,Thoh, M,Bhilwade, HN(2012).Schisandrin B exhibits anti-inflammatory activity through modulation of the redox-sensitive transcription factors Nrf2 and NF-kappaB.Free Radic Biol Med,53,1421-1430.
  18. Chen, JH,Huang, SM,Tan, TW,Lin, HY,Chen, PY,Yeh, WL(2012).Berberine induces heme oxygenase-1 up-regulation through phosphatidylinositol 3-kinase/AKT and NF-E2-related factor-2 signaling pathway in astrocytes.Int Immunopharmacol,12,94-100.
  19. Choi, KC,Jung, MG,Lee, YH,Yoon, JC,Kwon, SH,Kang, HB(2009).Epigallocatechin-3-gallate, a histone acetyltransferase inhibitor, inhibits EBV-induced B lymphocyte transformation via suppression of RelA acetylation.Cancer Res,69,583-592.
  20. Colotta, F,Allavena, P,Sica, A,Garlanda, C,Mantovani, A(2009).Cancer-related inflammation, the seventh hallmark of cancer: Links to genetic instability.Carcinogenesis,30,1073-1081.
  21. Croce, CM(2009).Causes and consequences of microRNA dysregulation in cancer.Nat Rev Genet,10,704-714.
  22. Cullinan, SB,Gordan, JD,Jin, J,Harper, JW,Diehl, JA(2004).The Keap1-BTB protein is an adaptor that bridges Nrf2 to a Cul3-based E3 ligase: Oxidative stress sensing by a Cul3-Keap1 ligase.Mol Cell Biol,24,8477-8486.
  23. Dalerba, P,Dylla, SJ,Park, IK,Liu, R,Wang, X,Cho, RW(2007).Phenotypic characterization of human colorectal cancer stem cells.Proc Natl Acad Sci U S A,104,10158-10163.
  24. Darley-Usmar, V,Halliwell, B(1996).Blood radicals: Reactive nitrogen species, reactive oxygen species, transition metal ions, and the vascular system.Pharm Res,13,649-662.
  25. De Marzo, AM,Platz, EA,Sutcliffe, S,Xu, J,Grönberg, H,Drake, CG(2007).Inflammation in prostate carcinogenesis.Nat Rev Cancer,7,256-269.
  26. Dick, JE(2008).Stem cell concepts renew cancer research.Blood,112,4793-4807.
  27. Dietz, BM,Liu, D,Hagos, GK,Yao, P,Schinkovitz, A,Pro, SM(2008).Angelica sinensis and its alkylphthalides induce the detoxification enzyme NAD(P)H: Quinone oxidoreductase 1 by alkylating Keap1.Chem Res Toxicol,21,1939-1948.
  28. Dinkova-Kostova, AT,Holtzclaw, WD,Cole, RN,Itoh, K,Wakabayashi, N,Katoh, Y(2002).Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants.Proc Natl Acad Sci U S A,99,11908-11913.
  29. Dinkova-Kostova, AT,Holtzclaw, WD,Wakabayashi, N(2005).Keap1, the sensor for electrophiles and oxidants that regulates the phase 2 response, is a zinc metalloprotein.Biochemistry,44,6889-6899.
  30. Egger, G,Liang, G,Aparicio, A,Jones, PA(2004).Epigenetics in human disease and prospects for epigenetic therapy.Nature,429,457-463.
  31. Emerit, J,Edeas, M,Bricaire, F(2004).Neurodegenerative diseases and oxidative stress.Biomed Pharmacother,58,39-46.
  32. Esteller, M(2002).CpG island hypermethylation and tumor suppressor genes: A booming present, a brighter future.Oncogene,21,5427-5440.
  33. Esteller, M(2008).Epigenetics in cancer.N Engl J Med,358,1148-1159.
  34. Fang, MZ,Chen, D,Sun, Y,Jin, Z,Christman, JK,Yang, CS(2005).Reversal of hypermethylation and reactivation of p16INK4a, RARbeta, and MGMT genes by genistein and other isoflavones from soy.Clin Cancer Res,11,7033-7041.
  35. Feinberg, AP,Tycko, B(2004).The history of cancer epigenetics.Nat Rev Cancer,4,143-153.
  36. Fenaux, P,Ades, L(2009).Review of azacitidine trials in Intermediate-2-and High-risk myelodysplastic syndromes.Leuk Res,33(Suppl 2),S7-SS11.
  37. Fidler, IJ,Hart, IR(1982).Biological diversity in metastatic neoplasms: Origins and implications.Science,217,998-1003.
  38. Fisher, CD,Augustine, LM,Maher, JM,Nelson, DM,Slitt, AL,Klaassen, CD(2007).Induction of drug-metabolizing enzymes by garlic and allyl sulfide compounds via activation of constitutive androstane receptor and nuclear factor E2-related factor 2.Drug Metab Dispos,35,995-1000.
  39. Fraga, MF,Ballestar, E,Villar-Garea, A,Boix-Chornet, M,Espada, J,Schotta, G(2005).Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer.Nat Genet,37,391-400.
  40. Fukai, T,Ushio-Fukai, M(2011).Superoxide dismutases: Role in redox signaling, vascular function, and diseases.Antioxid Redox Signal,15,1583-1606.
  41. Garcia-Manero, G,Assouline, S,Cortes, J,Estrov, Z,Kantarjian, H,Yang, H(2008).Phase 1 study of the oral isotype specific histone deacetylase inhibitor MGCD0103 in leukemia.Blood,112,981-989.
  42. Garg, A,Aggarwal, BB(2002).Nuclear transcription factor-kappaB as a target for cancer drug development.Leukemia,16,1053-1068.
  43. Gerhauser, C(2013).Cancer Chemoprevention and Nutri-Epigenetics: State of the Art and Future Challenges.Top Curr Chem,329,73-132.
  44. Ginestier, C,Wicinski, J,Cervera, N,Monville, F,Finetti, P,Bertucci, F(2009).Retinoid signaling regulates breast cancer stem cell differentiation.Cell Cycle,8,3297-3302.
  45. Giudice, A,Montella, M(2006).Activation of the Nrf2-ARE signaling pathway: A promising strategy in cancer prevention.Bioessays,28,169-181.
  46. Greten, FR,Eckmann, L,Greten, TF,Park, JM,Li, ZW,Egan, LJ(2004).IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer.Cell,118,285-296.
  47. Gum, SI,Jo, SJ,Ahn, SH,Kim, SG,Kim, JT,Shin, HM(2007).The potent protective effect of wild ginseng (Panax ginseng C.A. Meyer) against benzo[alpha]pyrene-induced toxicity through metabolic regulation of CYP1A1 and GSTs.J Ethnopharmacol,112,568-576.
  48. Guzman, ML,Rossi, RM,Neelakantan, S,Li, X,Corbett, CA,Hassane, DC(2007).An orally bioavailable parthenolide analog selectively eradicates acute myelogenous leukemia stem and progenitor cells.Blood,110,4427-4435.
  49. Hamburger, AW,Salmon, SE(1977).Primary bioassay of human tumor stem cells.Science,197,461-463.
  50. Han, ZG(2010).Epigenetic analysis in the search for tumor suppressor genes.Epigenomics,2,489-493.
  51. Hassane, DC,Guzman, ML,Corbett, C,Li, X,Abboud, R,Young, F(2008).Discovery of agents that eradicate leukemia stem cells using an in silico screen of public gene expression data.Blood,111,5654-5662.
  52. Heiss, E,Herhaus, C,Klimo, K,Bartsch, H,Gerhauser, C(2001).Nuclear factor kappa B is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms.J Biol Chem,276,32008-32015.
  53. Hsieh, TC,Wu, JM(2011).Suppression of proliferation and oxidative stress by extracts of Ganoderma lucidum in the ovarian cancer cell line OVCAR-3.Int J Mol Med,28,1065-1069.
  54. Hu, R,Saw, CL,Yu, R,Kong, AN(2010).Regulation of NF-E2-related factor 2 signaling for cancer chemoprevention: Antioxidant coupled with antiinflammatory.Antioxid Redox Signal,13,1679-1698.
  55. Hu, R,Shen, G,Yerramilli, UR,Lin, W,Xu, C,Nair, S(2006).In vivo pharmacokinetics, activation of MAPK signaling and induction of phase II/III drug metabolizing enzymes/transporters by cancer chemopreventive compound BHA in the mice.Arch Pharm Res,29,911-920.
  56. Huang, HC,Nguyen, T,Pickett, CB(2002).Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant response element-mediated transcription.J Biol Chem,277,42769-42774.
  57. Huang, HC,Nguyen, T,Pickett, CB(2000).Regulation of the antioxidant response element by protein kinase C-mediated phosphorylation of NF-E2-related factor 2.Proc Natl Acad Sci U S A,97,12475-12480.
  58. Hwang, YP,Jeong, HG(2008).Mechanism of phytoestrogen puerarin-mediated cytoprotection following oxidative injury: Estrogen receptor-dependent up-regulation of PI3K/Akt and HO-1.Toxicol Appl Pharmacol,233,371-381.
  59. Inoue, J,Kerr, LD,Kakizuka, A,Verma, IM(1992).I kappa B gamma, a 70 kd protein identical to the C-terminal half of p110 NF-kappa B: a new member of the I kappa B family.Cell,68,1109-1120.
  60. Issa, JP(2007).DNA methylation as a therapeutic target in cancer.Clin Cancer Res,13,1634-1637.
  61. Issa, JP,Kantarjian, HM(2009).Targeting DNA methylation.Clin Cancer Res,15,3938-3946.
  62. Jha, AK,Nikbakht, M,Parashar, G,Shrivastava, A,Capalash, N,Kaur, J(2010).Reversal of hypermethylation and reactivation of the RARbeta2 gene by natural compounds in cervical cancer cell lines.Folia Biol,56,195-200.
  63. Jomova, K,Vondrakova, D,Lawson, M,Valko, M(2010).Metals, oxidative stress and neurodegenerative disorders.Mol Cell Biochem,345,91-104.
  64. Jung, KA,Kwak, MK(2010).The Nrf2 system as a potential target for the development of indirect antioxidants.Molecules,15,7266-7291.
  65. Kakarala, M,Brenner, DE,Korkaya, H,Cheng, C,Tazi, K,Ginestier, C(2010).Targeting breast stem cells with the cancer preventive compounds curcum5in and piperine.Breast Cancer Res Treat,122,777-785.
  66. Kang, KW,Choi, SH,Kim, SG(2002).Peroxynitrite activates NF-E2-related factor 2/antioxidant response element through the pathway of phosphatidylinositol 3-kinase: The role of nitric oxide synthase in rat glutathione S-transferase A2 induction.Nitric Oxide,7,244-253.
  67. Kang, KW,Lee, SJ,Park, JW,Kim, SG(2002).Phosphatidylinositol 3-kinase regulates nuclear translocation of NF-E2-related factor 2 through actin rearrangement in response to oxidative stress.Mol Pharmacol,62,1001-1010.
  68. Karin, M,Ben-Neriah, Y(2000).Phosphorylation meets ubiquitination: The control of NF-[kappa]B activity.Annu Rev Immunol,18,621-663.
  69. Kensler, TW,Wakabayashi, N,Biswal, S(2007).Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway.Annu Rev Pharmacol Toxicol,47,89-116.
  70. Keum, YS,Yu, S,Chang, PP,Yuan, X,Kim, JH,Xu, C(2006).Mechanism of Action of Sulforaphane: Inhibition of p38 Mitogen-Activated Protein Kinase Isoforms Contributing to the Induction of Antioxidant Response Element-Mediated Heme Oxygenase-1 in Human Hepatoma HepG2 Cells.Cancer Res,66,8804-8813.
  71. Khor, TO,Huang, Y,Wu, TY,Shu, L,Lee, J,Kong, AN(2011).Pharmacodynamics of curcumin as DNA hypomethylation agent in restoring the expression of Nrf2 via promoter CpGs demethylation.Biochem Pharmacol,82,1073-1078.
  72. Khor, TO,Yu, S,Barve, A,Hao, X,Hong, JL,Lin, W(2009).Dietary feeding of dibenzoylmethane inhibits prostate cancer in transgenic adenocarcinoma of the mouse prostate model.Cancer Res,69,7096-7102.
  73. Kikuno, N,Shiina, H,Urakami, S,Kawamoto, K,Hirata, H,Tanaka, Y(2008).Genistein mediated histone acetylation and demethylation activates tumor suppressor genes in prostate cancer cells.Int J Cancer,123,552-560.
  74. Kim, KC,Kang, KA,Zhang, R,Piao, MJ,Kim, GY,Kang, MY(2010).Up-regulation of Nrf2-mediated heme oxygenase-1 expression by eckol, a phlorotannin compound, through activation of Erk and PI3K/Akt.Int J Biochem Cell Biol,42,297-305.
  75. Kim, YH,Choi, JH,Rim, HK,Kang, HJ,Chang, SG,Park, JH(2011).23-Hydroxytormentic acid and niga-ichgoside f(1) isolated from Rubus coreanus attenuate cisplatin-induced cytotoxicity by reducing oxidative stress in renal epithelial LLC-PK(1) cells.Biol Pharm Bull,34,906-911.
  76. Kim, YJ,Ahn, JY,Liang, P,Ip, C,Zhang, Y,Park, YM(2007).Human prx1 gene is a target of Nrf2 and is up-regulated by hypoxia/reoxygenation: Implication to tumor biology.Cancer Res,67,546-554.
  77. Kim, YS,Farrar, W,Colburn, NH,Milner, JA(2012).Cancer stem cells: Potential target for bioactive food components.J Nutr Biochem,23,691-698.
  78. Klose, RJ,Bird, AP(2006).Genomic DNA methylation: The mark and its mediators.Trends Biochem Sci,31,89-97.
  79. Kojo, S(2004).Vitamin C: Basic metabolism and its function as an index of oxidative stress.Curr Med Chem,11,1041-1064.
  80. Korkaya, H,Paulson, A,Charafe-Jauffret, E,Ginestier, C,Brown, M,Dutcher, J(2009).Regulation of mammary stem/progenitor cells by PTEN/Akt/beta-catenin signaling.PLoS Biol,7,e1000121.
  81. Kouzarides, T(2007).Chromatin modifications and their function.Cell,128,693-705.
  82. Lambert, JD,Sang, S,Hong, J,Yang, CS(2010).Anticancer and anti-inflammatory effects of cysteine metabolites of the green tea polyphenol, (-)-epigallocatechin-3-gallate.J Agric Food Chem,58,10016-10019.
  83. Lapidot, T,Sirard, C,Vormoor, J,Murdoch, B,Hoang, T,Caceres-Cortes, J(1994).A cell initiating human acute myeloid leukaemia after transplantation into SCID mice.Nature,367,645-648.
  84. Lau, A,Villeneuve, NF,Sun, Z,Wong, PK,Zhang, DD(2008).Dual roles of Nrf2 in cancer.Pharmacol Res,58,262-270.
  85. Le, XF,Merchant, O,Bast, RC,Calin, GA(2010).The Roles of MicroRNAs in the Cancer Invasion-Metastasis Cascade.Cancer Microenviron,3,137-147.
  86. Lee, JH,Khor, TO,Shu, L,Su, ZY,Fuentes, F,Kong, AN(2013).Dietary phytochemicals and cancer prevention: Nrf2 signaling, epigenetics, and cell death mechanisms in blocking cancer initiation and progression.Pharmacol Ther,137,153-171.
  87. Lee, JM,Hanson, JM,Chu, WA,Johnson, JA(2001).Phosphatidylinositol 3-kinase, not extracellular signal-regulated kinase, regulates activation of the antioxidant-responsive element in IMR-32 human neuroblastoma cells.J Biol Chem,276,20011-20016.
  88. Lee, SE,Jeong, SI,Yang, H,Jeong, SH,Jang, YP,Park, CS(2012).Extract of Salvia miltiorrhiza (Danshen) induces Nrf2-mediated heme oxygenase-1 expression as a cytoprotective action in RAW 264.7 macrophages.J Ethnopharmacol,139,541-548.
  89. Lee, YH,Kwak, J,Choi, HK,Choi, KC,Kim, S,Lee, J(2012).EGCG suppresses prostate cancer cell growth modulating acetylation of androgen receptor by anti-histone acetyltransferase activity.Int J Mol Med,30,69-74.
  90. Li, C,Heidt, DG,Dalerba, P,Burant, CF,Zhang, L,Adsay, V(2007).Identification of pancreatic cancer stem cells.Cancer Res,67,1030-1037.
  91. Li, W,Kong, AN(2009).Molecular mechanisms of Nrf2-mediated antioxidant response.Mol Carcinog,48,91-104.
  92. Li, Y,Zhang, T,Korkaya, H,Liu, S,Lee, HF,Newman, B(2010).Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells.Clin Cancer Res,16,2580-2590.
  93. Limon-Pacheco, JH,Gonsebatt, ME(2010).The glutathione system and its regulation by neurohormone melatonin in the central nervous system.Cent Nerv Syst Agents Med Chem,10,287-297.
  94. Lin, CH,Shen, YA,Hung, PH,Yu, YB,Chen, YJ(2012).Epigallocathechin gallate, polyphenol present in green tea, inhibits stem-like characteristics and epithelial-mesenchymal transition in nasopharyngeal cancer cell lines.BMC Complement Alternat Med,12,201.
  95. Lin, W,Wu, RT,Wu, T,Khor, TO,Wang, H,Kong, AN(2008).Sulforaphane suppressed LPS-induced inflammation in mouse peritoneal macrophages through Nrf2 dependent pathway.Biochem Pharmacol,76,967-973.
  96. Link, A,Balaguer, F,Goel, A(2010).Cancer chemoprevention by dietary polyphenols: Promising role for epigenetics.Biochem Pharmacol,80,1771-1792.
  97. Liu, S,Dontu, G,Wicha, MS(2005).Mammary stem cells, self-renewal pathways, and carcinogenesis.Breast Cancer Res,7,86-95.
  98. Lou, H,Jing, X,Ren, D,Wei, X,Zhang, X(2012).Eriodictyol protects against H(2)O(2)-induced neuron-like PC12 cell death through activation of Nrf2/ARE signaling pathway.Neurochem Int,61,251-257.
  99. Luedde, T,Beraza, N,Kotsikoris, V,van Loo, G,Nenci, A,De Vos, R(2007).Deletion of NEMO/IKKgamma in liver parenchymal cells causes steatohepatitis and hepatocellular carcinoma.Cancer Cell,11,119-132.
  100. Ma, X,Fang, Y,Beklemisheva, A,Dai, W,Feng, J,Ahmed, T(2006).Phenylhexyl isothiocyanate inhibits histone deacetylases and remodels chromatins to induce growth arrest in human leukemia cells.Int J Oncol,28,1287-1293.
  101. Mai, TT,Moon, J,Song, Y,Viet, PQ,Phuc, PV,Lee, JM(2012).Ginsenoside F2 induces apoptosis accompanied by protective autophagy in breast cancer stem cells.Cancer Lett,321,144-153.
  102. Majid, S,Kikuno, N,Nelles, J,Noonan, E,Tanaka, Y,Kawamoto, K(2008).Genistein induces the p21WAF1/CIP1 and p16INK4a tumor suppressor genes in prostate cancer cells by epigenetic mechanisms involving active chromatin modification.Cancer Res,68,2736-2744.
  103. Mamede, AC,Tavares, SD,Abrantes, AM,Trindade, J,Maia, JM,Botelho, MF(2011).The role of vitamins in cancer: A review.Nutr Cancer,63,479-494.
  104. Mansuy, D.(2011).Brief historical overview and recent progress on cytochromes P450: Adaptation of aerobic organisms to their chemical environment and new mechanisms of prodrug bioactivation.Ann Pharm Fr,69,62-69.
  105. Mantovani, A(2010).Mantovani A. Molecular pathways linking inflammation and cancer.Curr Mol Med,10,369-373.
  106. McCormack, MP,Young, LF,Vasudevan, S,de Graaf, CA,Codrington, R,Rabbitts, TH(2010).The Lmo2 oncogene initiates leukemia in mice by inducing thymocyte self-renewal.Science,327,879-883.
  107. McMahon, M,Itoh, K,Yamamoto, M,Chanas, SA,Henderson, CJ,McLellan, LI(2001).The Cap’n’Collar basic leucine zipper transcription factor Nrf2 (NF-E2 p45-related factor 2) controls both constitutive and inducible expression of intestinal detoxification and glutathione biosynthetic enzymes.Cancer Res,61,3299-3307.
  108. Meeran, SM,Ahmed, A,Tollefsbol, TO(2010).Epigenetic targets of bioactive dietary components for cancer prevention and therapy.Clin Epigenetics,1,101-116.
  109. Miao, W,Hu, L,Scrivens, PJ,Batist, G(2005).Transcriptional regulation of NF-E2 p45-related factor (NRF2) expression by the aryl hydrocarbon receptor-xenobiotic response element signaling pathway: Direct cross-talk between phase I and II drug-metabolizing enzymes.J Biol Chem,280,20340-20348.
  110. Nakaso, K,Yano, H,Fukuhara, Y,Takeshima, T,Wada-Isoe, K,Nakashima, K(2003).PI3K is a key molecule in the Nrf2-mediated regulation of antioxidative proteins by hemin in human neuroblastoma cells.FEBS Lett,546,181-184.
  111. Neelakandan, K,Babu, P,Nair, S(2012).Emerging roles for modulation of microRNA signatures in cancer chemoprevention.Curr Cancer Drug Targets,12,716-740.
  112. Nguyen, T,Sherratt, PJ,Huang, HC,Yang, CS,Pickett, CB(2003).Increased protein stability as a mechanism that enhances Nrf2-mediated transcriptional activation of the antioxidant response element. Degradation of Nrf2 by the 26 S proteasome.J Biol Chem,278,4536-4541.
  113. Nishikawa, M,Hashida, M,Takakura, Y(2009).Catalase delivery for inhibiting ROS-mediated tissue injury and tumor metastasis.Adv Drug Deliv Rev,61,319-326.
  114. Nowell, PC(1986).Mechanisms of tumor progression.Cancer Res,46,2203-2207.
  115. Numazawa, S,Ishikawa, M,Yoshida, A,Tanaka, S,Yoshida, T(2003).Atypical protein kinase C mediates activation of NF-E2-related factor 2 in response to oxidative stress.Am J Physiol Cell Physiol,285,C334-C342.
  116. Pahl, HL(1999).Activators and target genes of Rel/NF-kappaB transcription factors.Oncogene,18,6853-6866.
  117. Pan, MH,Lin-Shiau, SY,Lin, JK(2000).Comparative studies on the suppression of nitric oxide synthase by curcumin and its hydrogenated metabolites through down-regulation of IkappaB kinase and NFkappaB activation in macrophages.Biochem Pharmacol,60,1665-1676.
  118. Park, YH,Kim, SU,Lee, BK,Kim, HS,Song, IS,Shin, HJ(2012).Prx I suppresses K-ras-driven lung tumorigenesis by opposing redox-sensitive ERK/cyclin D1 pathway.Antioxid Redox Signal
  119. Parker, LP,Taylor, DD,Kesterson, J,Metzinger, DS,Gercel-Taylor, C(2009).Modulation of microRNA associated with ovarian cancer cells by genistein.Eur J Gynaecol Oncol,30,616-621.
  120. Poon, PY,Kwok, HH,Yue, PY,Yang, MS,Mak, NK,Wong, CK(2012).Cytoprotective effect of 20S-Rg3 on benzo[a]pyrene-induced DNA damage.Drug Metab Dispos,40,120-129.
  121. Prawan, A,Saw, CL,Khor, TO,Keum, YS,Yu, S,Hu, L(2009).Anti-NF-kappaB and anti-inflammatory activities of synthetic isothiocyanates: Effect of chemical structures and cellular signaling.Chem Biol Interact,179,202-211.
  122. Qin, S,Chen, J,Tanigawa, S,Hou, DX(2012).Gene expression profiling and pathway network analysis of hepatic metabolic enzymes targeted by baicalein.J Ethnopharmacol,140,131-140.
  123. Reya, T,Morrison, SJ,Clarke, MF,Weissman, IL(2001).Stem cells, cancer, and cancer stem cells.Nature,414,105-111.
  124. Rodova, M,Fu, J,Watkins, DN,Srivastava, RK,Shankar, S(2012).Sonic Hedgehog Signaling Inhibition Provides Opportunities for Targeted Therapy by Sulforaphane in Regulating Pancreatic Cancer Stem Cell Self-Renewal.PLoS ONE,7,e46083.
  125. Rushmore, TH,Pickett, CB(1993).Glutathione S-transferases, structure, regulation, and therapeutic implications.J Biol Chem,268,11475-11478.
  126. Saw, CL,Yang, AY,Cheng, DC,Boyanapalli, SS,Su, ZY,Khor, TO(2012).Pharmacodynamics of ginsenosides: Antioxidant activities, activation of Nrf2, and potential synergistic effects of combinations.Chem Res Toxicol,25,1574-1580.
  127. Schatton, T,Murphy, GF,Frank, NY,Yamaura, K,Waaga-Gasser, AM,Gasser, M(2008).Identification of cells initiating human melanomas.Nature,451,345-349.
  128. Sen, R,Baltimore, D(1986).Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism.Cell,47,921-928.
  129. Sethi, G,Sung, B,Aggarwal, BB(2008).Nuclear factor-kappaB activation: From bench to bedside.Exp Biol Med,233,21-31.
  130. Shackleton, M,Quintana, E,Fearon, ER,Morrison, SJ(2009).Heterogeneity in cancer: Cancer stem cells versus clonal evolution.Cell,138,822-829.
  131. Shen, G,Hebbar, V,Nair, S,Xu, C,Li, W,Lin, W(2004).Regulation of Nrf2 transactivation domain activity. The differential effects of mitogen-activated protein kinase cascades and synergistic stimulatory effect of Raf and CREB-binding protein.J Biol Chem,279,23052-23060.
  132. Shen, G,Kong, AN(2009).Nrf2 plays an important role in coordinated regulation of Phase II drug metabolism enzymes and Phase III drug transporters.Biopharm Drug Dispos,30,345-355.
  133. Shen, G,Xu, C,Hu, R,Jain, MR,Gopalkrishnan, A,Nair, S(2006).Modulation of nuclear factor E2-related factor 2-mediated gene expression in mice liver and small intestine by cancer chemopreventive agent curcumin.Mol Cancer Ther,5,39-51.
  134. Shin, S,Wakabayashi, J,Yates, MS,Wakabayashi, N,Dolan, PM,Aja, S(2009).Role of Nrf2 in prevention of high-fat diet-induced obesity by synthetic triterpenoid CDDO-imidazolide.Eur J Pharmacol,620,138-144.
  135. Shu, L,Khor, TO,Lee, JH,Boyanapalli, SS,Huang, Y,Wu, TY(2011).Epigenetic CpG demethylation of the promoter and reactivation of the expression of Neurog1 by curcumin in prostate LNCaP cells.AAPS J,13,606-614.
  136. Singh, SK,Clarke, ID,Terasaki, M,Bonn, VE,Hawkins, C,Squire, J(2003).Identification of a cancer stem cell in human brain tumors.Cancer Res,63,5821-5828.
  137. Smolarek, AK,So, JY,Thomas, PE,Lee, HJ,Paul, S,Dombrowski, A(2012).Dietary tocopherols inhibit cell proliferation, regulate expression of ERalpha, PPARgamma, and Nrf2, and decrease serum inflammatory markers during the development of mammary hyperplasia.Mol Carcinog
  138. Sriram, N,Kalayarasan, S,Sudhandiran, G(2009).Epigallocatechin-3-gallate augments antioxidant activities and inhibits inflammation during bleomycin-induced experimental pulmonary fibrosis through Nrf2-Keap1 signaling.Pulm Pharmacol Ther,22,221-236.
  139. Su, ZY,Shu, L,Khor, TO,Lee, JH,Fuentes, F,Kong, AN(2013).A Perspective on Dietary Phytochemicals and Cancer Chemoprevention: Oxidative Stress, Nrf2, and Epigenomics.Top Curr Chem,329,133-162.
  140. Sun, Q,Cong, R,Yan, H,Gu, H,Zeng, Y,Liu, N(2009).Genistein inhibits growth of human uveal melanoma cells and affects microRNA-27a and target gene expression.Oncol Rep,22,563-567.
  141. Sun, Z,Huang, Z,Zhang, DD(2009).Phosphorylation of Nrf2 at multiple sites by MAP kinases has a limited contribution in modulating the Nrf2-dependent antioxidant response.PLoS One,4,e6588.
  142. Tan, AC,Konczak, I,Sze, DM,Ramzan, I(2011).Molecular pathways for cancer chemoprevention by dietary phytochemicals.Nutr Cancer,63,495-505.
  143. Tang, SN,Singh, C,Nall, D,Meeker, D,Shankar, S,Srivastava, R(2010).The dietary bioflavonoid quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cell characteristics, invasion, migration and epithelial-mesenchymal transition.J Mol Signal,5,14.
  144. Traenckner, EB,Pahl, HL,Henkel, T,Schmidt, KN,Wilk, S,Baeuerle, PA(1995).Phosphorylation of human I kappa B-alpha on serines 32 and 36 controls I kappa B-alpha proteolysis and NF-kappa B activation in response to diverse stimuli.EMBO J,14,2876-2883.
  145. Tsai, WC,Hsu, PW,Lai, TC,Chau, GY,Lin, CW,Chen, CM(2009).MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma.Hepatology,49,1571-1582.
  146. Valko, M,Izakovic, M,Mazur, M,Rhodes, CJ,Telser, J(2004).Role of oxygen radicals in DNA damage and cancer incidence.Mol Cell Biochem,266,37-56.
  147. Valko, M,Rhodes, CJ,Moncol, J,Izakovic, M,Mazur, M(2006).Free radicals, metals and antioxidants in oxidative stress-induced cancer.Chem Biol Interact,160,1-40.
  148. Vanden Berghe, W(2012).Epigenetic impact of dietary polyphenols in cancer chemoprevention: lifelong remodeling of our epigenomes.Pharmacol Res,65,565-576.
  149. Vilas-Zornoza, A,Agirre, X,Martín-Palanco, V,Martín-Subero, JI,San José-Eneriz, E,Garate, L(2011).Frequent and simultaneous epigenetic inactivation of TP53 pathway genes in acute lymphoblastic leukemia.PLoS One,6,e17012.
  150. Volate, SR,Muga, SJ,Issa, AY,Nitcheva, D,Smith, T,Wargovich, MJ(2009).Epigenetic modulation of the retinoid X receptor alpha by green tea in the azoxymethane-Apc Min/+ mouse model of intestinal cancer.Mol Carcinog,48,920-933.
  151. Vrba, J,Orolinova, E,Ulrichova, J(2012).Induction of heme oxygenase-1 by Macleaya cordata extract and its constituent sanguinarine in RAW264.7 cells.Fitoterapia,83,329-335.
  152. Wang, H,Khor, TO,Shu, L,Su, ZY,Fuentes, F,Lee, JH,Kong, AN(2012).Plants against Cancer: A review on natural phytochemicals in preventing and treating cancers and their drug ability.Anticancer Agents Med Chem,12,1281-1305.
  153. Wang, LG,Beklemisheva, A,Liu, XM,Ferrari, AC,Feng, J,Chiao, JW(2007).Dual action on promoter demethylation and chromatin by an isothiocyanate restored GSTP1 silenced in prostate cancer.Mol Carcinog,46,24-31.
  154. Wang, LG,Liu, XM,Fang, Y,Dai, W,Chiao, FB,Puccio, GM(2008).Derepression of the p21 promoter in prostate cancer cells by an isothiocyanate via inhibition of HDACs and c-Myc.Int J Oncol,33,375-380.
  155. Wang, X,Hai, CX,Liang, X,Yu, SX,Zhang, W,Li, YL(2010).The protective effects of Acanthopanax senticosus Harms aqueous extracts against oxidative stress: Role of Nrf2 and antioxidant enzymes.J Ethnopharmacol,127,424-432.
  156. Wen, Z,Wang, Z,Wang, S,Ravula, R,Yang, L,Xu, J(2011).Discovery of molecular mechanisms of traditional Chinese medicinal formula Si-Wu-Tang using gene expression microarray and connectivity map.PLoS One,6,e18278.
  157. Xu, C,Shen, G,Yuan, X,Kim, JH,Gopalkrishnan, A,Keum, YS(2006).ERK and JNK signaling pathways are involved in the regulation of activator protein 1 and cell death elicited by three isothiocyanates in human prostate cancer PC-3 cells.Carcinogenesis,27,437-445.
  158. Yu, BP(1994).Cellular defenses against damage from reactive oxygen species.Physiol Rev,74,139-162.
  159. Zhang, DD(2006).Mechanistic studies of the Nrf2-Keap1 signaling pathway.Drug Metab Rev,38,769-789.
  160. Zhang, HS,Wang, SQ(2007).Nrf2 is involved in the effect of tanshinone IIA on intracellular redox status in human aortic smooth muscle cells.Biochem Pharmacol,73,1358-1366.
  161. Zipper, LM,Mulcahy, RT(2003).Erk activation is required for Nrf2 nuclear localization during pyrrolidine dithiocarbamate induction of glutamate cysteine ligase modulatory gene expression in HepG2 cells.Toxicol Sci,73,124-134.