Drug Delivery and Translational Research

, Volume 3, Issue 2, pp 165–182 | Cite as

Novel strategies targeting cancer stem cells through phytochemicals and their analogs

  • Prasad Dandawate
  • Subhash Padhye
  • Aamir Ahmad
  • Fazlul H. Sarkar
Review Article

Abstract

Cancer stem cells (CSCs) are cells that exist within a tumor with a capacity of self-renewal and an ability to differentiate, giving rise to heterogeneous populations of cancer cells. These cells are increasingly being implicated in resistance to conventional therapeutics and have also been implicated in tumor recurrence. Several cellular signaling pathways including Notch, Wnt, phosphoinositide-3-kinase–Akt–mammalian target of rapamycin pathways, and known markers such as CD44, CD133, CD166, ALDH, etc. have been associated with CSCs. Here, we have reviewed our current understanding of self-renewal pathways and factors that help in the survival of CSCs with special emphasis on those that have been documented to be modulated by well characterized natural agents such as curcumin, sulforaphane, resveratrol, genistein, and epigallocatechin gallate. With the inclusion of a novel derivative of curcumin, CDF, we showcase how natural agents can be effectively modified to increase their efficacy, particularly against CSCs. We hope that this article will generate interest among researchers for further mechanistic and clinical studies exploiting the cancer preventive and therapeutic role of nutraceuticals by targeted elimination of CSCs.

Keywords

Cancer stem cells Phytochemicals CDF Notch EMT 

References

  1. 1.
    Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61:212–36.PubMedCrossRefGoogle Scholar
  2. 2.
    Vogelstein B, Kinzler KW. Cancer genes and the pathways they control. Nat Med. 2004;10:789–99.PubMedCrossRefGoogle Scholar
  3. 3.
    Gomez-Veiga F, Marino A, Alvarez L, Rodriguez I, Fernandez C, Pertega S, Candal A. Brachytherapy for the treatment of recurrent prostate cancer after radiotherapy or radical prostatectomy. BJU Int. 2012;109 Suppl 1:17–21.PubMedCrossRefGoogle Scholar
  4. 4.
    Meguid RA, Hooker CM, Taylor JT, Kleinberg LR, Cattaneo SM, Sussman MS, Yang SC, Heitmiller RF, Forastiere AA, Brock MV. Recurrence after neoadjuvant chemoradiation and surgery for esophageal cancer: does the pattern of recurrence differ for patients with complete response and those with partial or no response? J Thorac Cardiovasc Surg. 2009;138:1309–17.PubMedCrossRefGoogle Scholar
  5. 5.
    Li Y, Laterra J. Cancer stem cells: distinct entities or dynamically regulated phenotypes? Cancer Res. 2012;72:576–80.PubMedCrossRefGoogle Scholar
  6. 6.
    Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer. 2005;5:275–84.PubMedCrossRefGoogle Scholar
  7. 7.
    Subramaniam D, Ramalingam S, Houchen CW, Anant S. Cancer stem cells: a novel paradigm for cancer prevention and treatment. Mini Rev Med Chem. 2010;10:359–71.PubMedCrossRefGoogle Scholar
  8. 8.
    Padhye S, Chavan D, Pandey S, Deshpande J, Swamy KV, Sarkar FH. Perspectives on chemopreventive and therapeutic potential of curcumin analogs in medicinal chemistry. Mini Rev Med Chem. 2010;10:372–87.PubMedCrossRefGoogle Scholar
  9. 9.
    Neves AR, Lucio M, Lima JL, Reis S. Resveratrol in medicinal chemistry: a critical review of its pharmacokinetics, drug-delivery, and membrane interactions. Curr Med Chem. 2012;19:1663–81.Google Scholar
  10. 10.
    Kong D, Wang Z, Sarkar SH, Li Y, Banerjee S, Saliganan A, Kim HR, Cher ML, Sarkar FH. Platelet-derived growth factor-D overexpression contributes to epithelial–mesenchymal transition of PC3 prostate cancer cells. Stem Cells. 2008;26:1425–35.PubMedCrossRefGoogle Scholar
  11. 11.
    Kong D, Banerjee S, Ahmad A, Li Y, Wang Z, Sethi S, Sarkar FH. Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells. PLoS One. 2010;5:e12445.PubMedCrossRefGoogle Scholar
  12. 12.
    Sethi S, Sarkar FH, Ahmed Q, Bandyopadhyay S, Nahleh ZA, Semaan A, Sakr W, Munkarah A, Li-Fehmi R. Molecular markers of epithelial-to-mesenchymal transition are associated with tumor aggressiveness in breast carcinoma. Transl Oncol. 2011;4:222–6.PubMedGoogle Scholar
  13. 13.
    Bao B, Wang Z, Ali S, Kong D, Banerjee S, Ahmad A, Li Y, Azmi AS, Miele L, Sarkar FH. Over-expression of FoxM1 leads to epithelial–mesenchymal transition and cancer stem cell phenotype in pancreatic cancer cells. J Cell Biochem. 2011;112:2296–306.PubMedCrossRefGoogle Scholar
  14. 14.
    Bao B, Wang Z, Ali S, Kong D, Li Y, Ahmad A, Banerjee S, Azmi AS, Miele L, Sarkar FH. Notch-1 induces epithelial–mesenchymal transition consistent with cancer stem cell phenotype in pancreatic cancer cells. Cancer Lett. 2011;307:26–36.PubMedCrossRefGoogle Scholar
  15. 15.
    Wang Z, Li Y, Kong D, Banerjee S, Ahmad A, Azmi AS, Ali S, Abbruzzese JL, Gallick GE, Sarkar FH. Acquisition of epithelial–mesenchymal transition phenotype of gemcitabine-resistant pancreatic cancer cells is linked with activation of the notch signaling pathway. Cancer Res. 2009;69:2400–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Wang Z, Li Y, Banerjee S, Sarkar FH. Emerging role of Notch in stem cells and cancer. Cancer Lett. 2009;279:8–12.PubMedCrossRefGoogle Scholar
  17. 17.
    Wang Z, Li Y, Ahmad A, Azmi AS, Kong D, Banerjee S, Sarkar FH. Targeting miRNAs involved in cancer stem cell and EMT regulation: an emerging concept in overcoming drug resistance. Drug Resist Updat. 2010;13:109–18.PubMedCrossRefGoogle Scholar
  18. 18.
    Wang Z, Li Y, Sarkar FH. Signaling mechanism(s) of reactive oxygen species in epithelial–mesenchymal transition reminiscent of cancer stem cells in tumor progression. Curr Stem Cell Res Ther. 2010;5:74–80.PubMedCrossRefGoogle Scholar
  19. 19.
    Bao B, Ali S, Kong D, Sarkar SH, Wang Z, Banerjee S, Aboukameel A, Padhye S, Philip PA, Sarkar FH. Anti-tumor activity of a novel compound-CDF is mediated by regulating miR-21, miR-200, and PTEN in pancreatic cancer. PLoS One. 2011;6:e17850.PubMedCrossRefGoogle Scholar
  20. 20.
    Wang Z, Li Y, Ahmad A, Banerjee S, Azmi AS, Kong D, Wojewoda C, Miele L, Sarkar FH. Down-regulation of Notch-1 is associated with Akt and FoxM1 in inducing cell growth inhibition and apoptosis in prostate cancer cells. J Cell Biochem. 2011;112:78–88.PubMedCrossRefGoogle Scholar
  21. 21.
    Kanwar SS, Yu Y, Nautiyal J, Patel BB, Padhye S, Sarkar FH, Majumdar AP. Difluorinated-curcumin (CDF): a novel curcumin analog is a potent inhibitor of colon cancer stem-like cells. Pharm Res. 2011;28:827–38.PubMedCrossRefGoogle Scholar
  22. 22.
    Sarkar FH, Li Y, Wang Z, Kong D, Ali S. Implication of microRNAs in drug resistance for designing novel cancer therapy. Drug Resist Updat. 2010;13:57–66.PubMedCrossRefGoogle Scholar
  23. 23.
    Li Y, Vandenboom TG, Kong D, Wang Z, Ali S, Philip PA, Sarkar FH. Up-regulation of miR-200 and let-7 by natural agents leads to the reversal of epithelial-to-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells. Cancer Res. 2009;69:6704–12.PubMedCrossRefGoogle Scholar
  24. 24.
    Kong D, Li Y, Wang Z, Sarkar FH. Cancer stem cells and epithelial-to-mesenchymal transition (EMT)-phenotypic cells: are they cousins or twins? Cancers (Basel). 2011;3:716–29.CrossRefGoogle Scholar
  25. 25.
    Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nat Rev Cancer. 2003;3:895–902.PubMedCrossRefGoogle Scholar
  26. 26.
    Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ, Heeschen C. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell. 2007;1:313–23.PubMedCrossRefGoogle Scholar
  27. 27.
    O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445:106–10.PubMedCrossRefGoogle Scholar
  28. 28.
    Zhou BB, Zhang H, Damelin M, Geles KG, Grindley JC, Dirks PB. Tumour-initiating cells: challenges and opportunities for anticancer drug discovery. Nat Rev Drug Discov. 2009;8:806–23.PubMedCrossRefGoogle Scholar
  29. 29.
    Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA. The epithelial–mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704–15.PubMedCrossRefGoogle Scholar
  30. 30.
    Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009;9:265–73.PubMedCrossRefGoogle Scholar
  31. 31.
    Wang Z, Li Y, Ahmad A, Banerjee S, Azmi AS, Kong D, Sarkar FH. Pancreatic cancer: understanding and overcoming chemoresistance. Nat Rev Gastroenterol Hepatol. 2011;8:27–33.PubMedCrossRefGoogle Scholar
  32. 32.
    Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene. 2010;29:4741–51.PubMedCrossRefGoogle Scholar
  33. 33.
    Thiery JP. Epithelial–mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002;2:442–54.PubMedCrossRefGoogle Scholar
  34. 34.
    Brabletz T, Jung A, Reu S, Porzner M, Hlubek F, Kunz-Schughart LA, Knuechel R, Kirchner T. Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc Natl Acad Sci U S A. 2001;98:10356–61.PubMedCrossRefGoogle Scholar
  35. 35.
    Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T. Opinion: migrating cancer stem cells—an integrated concept of malignant tumour progression. Nat Rev Cancer. 2005;5:744–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Lee JM, Dedhar S, Kalluri R, Thompson EW. The epithelial–mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol. 2006;172:973–81.PubMedCrossRefGoogle Scholar
  37. 37.
    Hollier BG, Evans K, Mani SA. The epithelial-to-mesenchymal transition and cancer stem cells: a coalition against cancer therapies. J Mammary Gland Biol Neoplasia. 2009;14:29–43.PubMedCrossRefGoogle Scholar
  38. 38.
    Hugo H, Ackland ML, Blick T, Lawrence MG, Clements JA, Williams ED, Thompson EW. Epithelial–mesenchymal and mesenchymal–epithelial transitions in carcinoma progression. J Cell Physiol. 2007;213:374–83.PubMedCrossRefGoogle Scholar
  39. 39.
    Christiansen JJ, Rajasekaran AK. Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res. 2006;66:8319–26.PubMedCrossRefGoogle Scholar
  40. 40.
    Chaffer CL, Brennan JP, Slavin JL, Blick T, Thompson EW, Williams ED. Mesenchymal-to-epithelial transition facilitates bladder cancer metastasis: role of fibroblast growth factor receptor-2. Cancer Res. 2006;66:11271–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Irie HY, Pearline RV, Grueneberg D, Hsia M, Ravichandran P, Kothari N, Natesan S, Brugge JS. Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial–mesenchymal transition. J Cell Biol. 2005;171:1023–34.PubMedCrossRefGoogle Scholar
  42. 42.
    Moustakas A, Heldin CH. Signaling networks guiding epithelial–mesenchymal transitions during embryogenesis and cancer progression. Cancer Sci. 2007;98:1512–20.PubMedCrossRefGoogle Scholar
  43. 43.
    Thiery JP, Sleeman JP. Complex networks orchestrate epithelial–mesenchymal transitions. Nat Rev Mol Cell Biol. 2006;7:131–42.PubMedCrossRefGoogle Scholar
  44. 44.
    Schmalhofer O, Brabletz S, Brabletz T. E-cadherin, beta-catenin, and ZEB1 in malignant progression of cancer. Cancer Metastasis Rev. 2009;28:151–66.PubMedCrossRefGoogle Scholar
  45. 45.
    Berx G, Raspe E, Christofori G, Thiery JP, Sleeman JP. Pre-EMTing metastasis? Recapitulation of morphogenetic processes in cancer. Clin Exp Metastasis. 2007;24:587–97.PubMedCrossRefGoogle Scholar
  46. 46.
    Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10:593–601.PubMedCrossRefGoogle Scholar
  47. 47.
    Kasper S. Stem cells: the root of prostate cancer? J Cell Physiol. 2008;216:332–6.PubMedCrossRefGoogle Scholar
  48. 48.
    Kasper S. Identification, characterization, and biological relevance of prostate cancer stem cells from clinical specimens. Urol Oncol. 2009;27:301–3.PubMedCrossRefGoogle Scholar
  49. 49.
    Marian CO, Shay JW. Prostate tumor-initiating cells: a new target for telomerase inhibition therapy? Biochim Biophys Acta. 2009;1792:289–96.PubMedCrossRefGoogle Scholar
  50. 50.
    Peter ME. Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression. Cell Cycle. 2009;8:843–52.PubMedCrossRefGoogle Scholar
  51. 51.
    Santisteban M, Reiman JM, Asiedu MK, Behrens MD, Nassar A, Kalli KR, Haluska P, Ingle JN, Hartmann LC, Manjili MH, Radisky DC, Ferrone S, Knutson KL. Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells. Cancer Res. 2009;69:2887–95.PubMedCrossRefGoogle Scholar
  52. 52.
    Armstrong AJ, Marengo MS, Oltean S, Kemeny G, Bitting RL, Turnbull JD, Herold CI, Marcom PK, George DJ, Garcia-Blanco MA. Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers. Mol Cancer Res. 2011;9:997–1007.PubMedCrossRefGoogle Scholar
  53. 53.
    Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367:645–8.PubMedCrossRefGoogle Scholar
  54. 54.
    Al-Hajj M, Wicha MS, Ito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003;100:3983–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De MR. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445:111–5.PubMedCrossRefGoogle Scholar
  56. 56.
    Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003;63:5821–8.PubMedGoogle Scholar
  57. 57.
    Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB. Identification of human brain tumour initiating cells. Nature. 2004;432:396–401.PubMedCrossRefGoogle Scholar
  58. 58.
    Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67:1030–7.PubMedCrossRefGoogle Scholar
  59. 59.
    Eguchi S, Kanematsu T, Arii S, Omata M, Kudo M, Sakamoto M, Takayasu K, Makuuchi M, Matsuyama Y, Monden M. Recurrence-free survival more than 10 years after liver resection for hepatocellular carcinoma. Br J Surg. 2011;98:552–7.PubMedCrossRefGoogle Scholar
  60. 60.
    Zhu Z, Hao X, Yan M, Yao M, Ge C, Gu J, Li J. Cancer stem/progenitor cells are highly enriched in CD133+CD44+ population in hepatocellular carcinoma. Int J Cancer. 2010;126:2067–78.PubMedCrossRefGoogle Scholar
  61. 61.
    Curley MD, Therrien VA, Cummings CL, Sergent PA, Koulouris CR, Friel AM, Roberts DJ, Seiden MV, Scadden DT, Rueda BR, Foster R. CD133 expression defines a tumor initiating cell population in primary human ovarian cancer. Stem Cells. 2009;27:2875–83.PubMedGoogle Scholar
  62. 62.
    Suzuki S, Terauchi M, Umezu T, Kajiyama H, Shibata K, Nawa A, Kikkawa F. Identification and characterization of cancer stem cells in ovarian yolk sac tumors. Cancer Sci. 2010;101:2179–85.PubMedCrossRefGoogle Scholar
  63. 63.
    Ning ZF, Huang YJ, Lin TX, Zhou YX, Jiang C, Xu KW, Huang H, Yin XB, Huang J. Subpopulations of stem-like cells in side population cells from the human bladder transitional cell cancer cell line T24. J Int Med Res. 2009;37:621–30.PubMedGoogle Scholar
  64. 64.
    She JJ, Zhang PG, Wang ZM, Gan WM, Che XM. Identification of side population cells from bladder cancer cells by DyeCycle Violet staining. Cancer Biol Ther. 2008;7:1663–8.PubMedCrossRefGoogle Scholar
  65. 65.
    Janikova M, Skarda J, Dziechciarkova M, Radova L, Chmelova J, Krejci V, Sedlakova E, Zapletalova J, Langova K, Klein J, Grygarkova I, Kolek V. Identification of CD133+/nestin+ putative cancer stem cells in non-small cell lung cancer. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2010;154:321–6.PubMedCrossRefGoogle Scholar
  66. 66.
    Leung EL, Fiscus RR, Tung JW, Tin VP, Cheng LC, Sihoe AD, Fink LM, Ma Y, Wong MP. Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties. PLoS One. 2010;5:e14062.PubMedCrossRefGoogle Scholar
  67. 67.
    Moriyama T, Ohuchida K, Mizumoto K, Cui L, Ikenaga N, Sato N, Tanaka M. Enhanced cell migration and invasion of CD133+ pancreatic cancer cells cocultured with pancreatic stromal cells. Cancer. 2010;116:3357–68.PubMedCrossRefGoogle Scholar
  68. 68.
    Bracken CP, Gregory PA, Khew-Goodall Y, Goodall GJ. The role of microRNAs in metastasis and epithelial–mesenchymal transition. Cell Mol Life Sci. 2009;66:1682–99.PubMedCrossRefGoogle Scholar
  69. 69.
    Gibbons DL, Lin W, Creighton CJ, Rizvi ZH, Gregory PA, Goodall GJ, Thilaganathan N, Du L, Zhang Y, Pertsemlidis A, Kurie JM. Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression. Genes Dev. 2009;23:2140–51.PubMedCrossRefGoogle Scholar
  70. 70.
    Gregory PA, Bracken CP, Bert AG, Goodall GJ. MicroRNAs as regulators of epithelial–mesenchymal transition. Cell Cycle. 2008;7:3112–8.PubMedCrossRefGoogle Scholar
  71. 71.
    Wellner U, Schubert J, Burk UC, Schmalhofer O, Zhu F, Sonntag A, Waldvogel B, Vannier C, Darling D, zur Hausen A, Brunton VG, Morton J, Sansom O, Schuler J, Stemmler MP, Herzberger C, Hopt U, Keck T, Brabletz S, Brabletz T. The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol. 2009;11:1487–95.PubMedCrossRefGoogle Scholar
  72. 72.
    Ahmad A, Aboukameel A, Kong D, Wang Z, Sethi S, Chen W, Sarkar FH, Raz A. Phosphoglucose isomerase/autocrine motility factor mediates epithelial–mesenchymal transition regulated by miR-200 in breast cancer cells. Cancer Res. 2011;71:3400–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Korpal M, Lee ES, Hu G, Kang Y. The miR-200 family inhibits epithelial–mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem. 2008;283:14910–4.PubMedCrossRefGoogle Scholar
  74. 74.
    Park SM, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008;22:894–907.PubMedCrossRefGoogle Scholar
  75. 75.
    Vetter G, Saumet A, Moes M, Vallar L, Le BA, Laurini C, Sabbah M, Arar K, Theillet C, Lecellier CH, Friederich E. miR-661 expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1 and StarD10 messengers. Oncogene. 2010;29:4436–48.PubMedCrossRefGoogle Scholar
  76. 76.
    Stinson S, Lackner MR, Adai AT, Yu N, Kim HJ, O’Brien C, Spoerke J, Jhunjhunwala S, Boyd Z, Januario T, Newman RJ, Yue P, Bourgon R, Modrusan Z, Stern HM, Warming S, de Sauvage FJ, Amler L, Yeh RF, Dornan D. TRPS1 targeting by miR-221/222 promotes the epithelial-to-mesenchymal transition in breast cancer. Sci Signal. 2011;4:ra41.PubMedCrossRefGoogle Scholar
  77. 77.
    Li QQ, Chen ZQ, Cao XX, Xu JD, Xu JW, Chen YY, Wang WJ, Chen Q, Tang F, Liu XP, Xu ZD. Involvement of NF-kappaB/miR-448 regulatory feedback loop in chemotherapy-induced epithelial–mesenchymal transition of breast cancer cells. Cell Death Differ. 2011;18:16–25.PubMedCrossRefGoogle Scholar
  78. 78.
    Peng X, Guo W, Liu T, Wang X, Tu X, Xiong D, Chen S, Lai Y, Du H, Chen G, Liu G, Tang Y, Huang S, Zou X. Identification of miRs-143 and -145 that is associated with bone metastasis of prostate cancer and involved in the regulation of EMT. PLoS One. 2011;6:e20341.PubMedCrossRefGoogle Scholar
  79. 79.
    Lulla RR, Costa FF, Bischof JM, Chou PM, de Bonaldo F, Vanin EF, Soares MB. Identification of differentially expressed MicroRNAs in osteosarcoma. Sarcoma. 2011;2011:732690.PubMedCrossRefGoogle Scholar
  80. 80.
    Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P, Qian D, Diehn M, Liu H, Panula SP, Chiao E, Dirbas FM, Somlo G, Pera RA, Lao K, Clarke MF. Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell. 2009;138:592–603.PubMedCrossRefGoogle Scholar
  81. 81.
    Jung DE, Wen J, Oh T, Song SY. Differentially expressed microRNAs in pancreatic cancer stem cells. Pancreas. 2011;40:1180–7.PubMedCrossRefGoogle Scholar
  82. 82.
    Hao J, Zhang S, Zhou Y, Hu X, Shao C. MicroRNA 483-3p suppresses the expression of DPC4/Smad4 in pancreatic cancer. FEBS Lett. 2011;585:207–13.PubMedCrossRefGoogle Scholar
  83. 83.
    Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, Patrawala L, Yan H, Jeter C, Honorio S, Wiggins JF, Bader AG, Fagin R, Brown D, Tang DG. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med. 2011;17:211–5.PubMedCrossRefGoogle Scholar
  84. 84.
    Kong D, Heath E, Chen W, Cher M, Powell I, Heilbrun L, Li Y, Ali S, Sethi S, Hassan O, Hwang C, Gupta N, Chitale D, Sakr WA, Menon M, Sarkar FH. Epigenetic silencing of miR-34a in human prostate cancer cells and tumor tissue specimens can be reversed by BR-DIM treatment. Am J Transl Res. 2012;4:14–23.PubMedGoogle Scholar
  85. 85.
    Miele L. Notch signaling. Clin Cancer Res. 2006;12:1074–9.PubMedCrossRefGoogle Scholar
  86. 86.
    Weng AP, Lau A. Notch signaling in T-cell acute lymphoblastic leukemia. Future Oncol. 2005;1:511–9.PubMedCrossRefGoogle Scholar
  87. 87.
    Sjolund J, Manetopoulos C, Stockhausen MT, Axelson H. The Notch pathway in cancer: differentiation gone awry. Eur J Cancer. 2005;41:2620–9.PubMedCrossRefGoogle Scholar
  88. 88.
    Li JL, Harris AL. Notch signaling from tumor cells: a new mechanism of angiogenesis. Cancer Cell. 2005;8:1–3.PubMedCrossRefGoogle Scholar
  89. 89.
    Bray SJ. Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol. 2006;7:678–89.PubMedCrossRefGoogle Scholar
  90. 90.
    Real PJ, Ferrando AA. NOTCH inhibition and glucocorticoid therapy in T-cell acute lymphoblastic leukemia. Leukemia. 2009;23:1374–7.PubMedCrossRefGoogle Scholar
  91. 91.
    Qiao L, Wong BC. Role of Notch signaling in colorectal cancer. Carcinogenesis. 2009;30:1979–86.PubMedCrossRefGoogle Scholar
  92. 92.
    Sandy AR, Maillard I. Notch signaling in the hematopoietic system. Expert Opin Biol Ther. 2009;9:1383–98.PubMedCrossRefGoogle Scholar
  93. 93.
    Wang M, Xue L, Cao Q, Lin Y, Ding Y, Yang P, Che L. Expression of Notch1, Jagged1 and beta-catenin and their clinicopathological significance in hepatocellular carcinoma. Neoplasma. 2009;56:533–41.PubMedCrossRefGoogle Scholar
  94. 94.
    Gao J, Chen Y, Wu KC, Liu J, Zhao YQ, Pan YL, Du R, Zheng GR, Xiong YM, Xu HL, Fan DM. RUNX3 directly interacts with intracellular domain of Notch1 and suppresses Notch signaling in hepatocellular carcinoma cells. Exp Cell Res. 2010;316:149–57.PubMedCrossRefGoogle Scholar
  95. 95.
    Wang C, Qi R, Li N, Wang Z, An H, Zhang Q, Yu Y, Cao X. Notch1 signaling sensitizes tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human hepatocellular carcinoma cells by inhibiting Akt/Hdm2-mediated p53 degradation and up-regulating p53-dependent DR5 expression. J Biol Chem. 2009;284:16183–90.PubMedCrossRefGoogle Scholar
  96. 96.
    Dotto GP. Notch tumor suppressor function. Oncogene. 2008;27:5115–23.PubMedCrossRefGoogle Scholar
  97. 97.
    Nicolas M, Wolfer A, Raj K, Kummer JA, Mill P, van Noort M, Hui CC, Clevers H, Dotto GP, Radtke F. Notch1 functions as a tumor suppressor in mouse skin. Nat Genet. 2003;33:416–21.PubMedCrossRefGoogle Scholar
  98. 98.
    De La OJ, Murtaugh LC. Notch and Kras in pancreatic cancer: at the crossroads of mutation, differentiation and signaling. Cell Cycle. 2009;8:1860–4.CrossRefGoogle Scholar
  99. 99.
    Osipo C, Golde TE, Osborne BA, Miele LA. Off the beaten pathway: the complex cross talk between Notch and NF-kappaB. Lab Invest. 2008;88:11–7.PubMedCrossRefGoogle Scholar
  100. 100.
    Sundaram MV. The love-hate relationship between Ras and Notch. Genes Dev. 2005;19:1825–39.PubMedCrossRefGoogle Scholar
  101. 101.
    Wang Z, Sengupta R, Banerjee S, Li Y, Zhang Y, Rahman KM, Aboukameel A, Mohammad R, Majumdar AP, Abbruzzese JL, Sarkar FH. Epidermal growth factor receptor-related protein inhibits cell growth and invasion in pancreatic cancer. Cancer Res. 2006;66:7653–60.PubMedCrossRefGoogle Scholar
  102. 102.
    Wang Z, Kong D, Banerjee S, Li Y, Adsay NV, Abbruzzese J, Sarkar FH. Down-regulation of platelet-derived growth factor-D inhibits cell growth and angiogenesis through inactivation of Notch-1 and nuclear factor-kappaB signaling. Cancer Res. 2007;67:11377–85.PubMedCrossRefGoogle Scholar
  103. 103.
    Weijzen S, Rizzo P, Braid M, Vaishnav R, Jonkheer SM, Zlobin A, Osborne BA, Gottipati S, Aster JC, Hahn WC, Rudolf M, Siziopikou K, Kast WM, Miele L. Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells. Nat Med. 2002;8:979–86.PubMedCrossRefGoogle Scholar
  104. 104.
    Wang Z, Li Y, Kong D, Ahmad A, Banerjee S, Sarkar FH. Cross-talk between miRNA and Notch signaling pathways in tumor development and progression. Cancer Lett. 2010;292:141–8.PubMedCrossRefGoogle Scholar
  105. 105.
    Rizzo P, Osipo C, Foreman K, Golde T, Osborne B, Miele L. Rational targeting of Notch signaling in cancer. Oncogene. 2008;27:5124–31.PubMedCrossRefGoogle Scholar
  106. 106.
    Song LL, Peng Y, Yun J, Rizzo P, Chaturvedi V, Weijzen S, Kast WM, Stone PJ, Santos L, Loredo A, Lendahl U, Sonenshein G, Osborne B, Qin JZ, Pannuti A, Nickoloff BJ, Miele L. Notch-1 associates with IKKalpha and regulates IKK activity in cervical cancer cells. Oncogene. 2008;27:5833–44.PubMedCrossRefGoogle Scholar
  107. 107.
    Sharma RP, Chopra VL. Effect of the Wingless (wg1) mutation on wing and haltere development in Drosophila melanogaster. Dev Biol. 1976;48:461–5.PubMedCrossRefGoogle Scholar
  108. 108.
    Nusse R, van Ooyen A, Cox D, Fung YK, Varmus H. Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15. Nature. 1984;307:131–6.PubMedCrossRefGoogle Scholar
  109. 109.
    Kohn AD, Moon RT. Wnt and calcium signaling: beta-catenin-independent pathways. Cell Calcium. 2005;38:439–46.PubMedCrossRefGoogle Scholar
  110. 110.
    Woll PS, Morris JK, Painschab MS, Marcus RK, Kohn AD, Biechele TL, Moon RT, Kaufman DS. Wnt signaling promotes hematoendothelial cell development from human embryonic stem cells. Blood. 2008;111:122–31.PubMedCrossRefGoogle Scholar
  111. 111.
    Angers S, Moon RT. Proximal events in Wnt signal transduction. Nat Rev Mol Cell Biol. 2009;10:468–77.PubMedGoogle Scholar
  112. 112.
    Semenov MV, Habas R, Macdonald BT, He X. SnapShot: noncanonical Wnt signaling pathways. Cell. 2007;131:1378.PubMedCrossRefGoogle Scholar
  113. 113.
    Macdonald BT, Semenov MV, He X. SnapShot: Wnt/beta-catenin signaling. Cell. 2007;131:1204.PubMedCrossRefGoogle Scholar
  114. 114.
    De A. Wnt/Ca2+ signaling pathway: a brief overview. Acta Biochim Biophys Sin (Shanghai). 2011;43:745–56.CrossRefGoogle Scholar
  115. 115.
    Leris AC, Roberts TR, Jiang WG, Newbold RF, Mokbel K. WNT5A expression in human breast cancer. Anticancer Res. 2005;25:731–4.PubMedGoogle Scholar
  116. 116.
    Kremenevskaja N, von Wasielewski R, Rao AS, Schofl C, Andersson T, Brabant G. Wnt-5a has tumor suppressor activity in thyroid carcinoma. Oncogene. 2005;24:2144–54.PubMedCrossRefGoogle Scholar
  117. 117.
    MacLeod RJ, Hayes M, Pacheco I. Wnt5a secretion stimulated by the extracellular calcium-sensing receptor inhibits defective Wnt signaling in colon cancer cells. Am J Physiol Gastrointest Liver Physiol. 2007;293:G403–11.PubMedCrossRefGoogle Scholar
  118. 118.
    Wang Q, Symes AJ, Kane CA, Freeman A, Nariculam J, Munson P, Thrasivoulou C, Masters JR, Ahmed A. A novel role for Wnt/Ca2+ signaling in actin cytoskeleton remodeling and cell motility in prostate cancer. PLoS One. 2010;5:e10456.PubMedCrossRefGoogle Scholar
  119. 119.
    Yamamoto H, Oue N, Sato A, Hasegawa Y, Yamamoto H, Matsubara A, Yasui W, Kikuchi A. Wnt5a signaling is involved in the aggressiveness of prostate cancer and expression of metalloproteinase. Oncogene. 2010;29:2036–46.PubMedCrossRefGoogle Scholar
  120. 120.
    Weeraratna AT, Jiang Y, Hostetter G, Rosenblatt K, Duray P, Bittner M, Trent JM. Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. Cancer Cell. 2002;1:279–88.PubMedCrossRefGoogle Scholar
  121. 121.
    Pukrop T, Klemm F, Hagemann T, Gradl D, Schulz M, Siemes S, Trumper L, Binder C. Wnt 5a signaling is critical for macrophage-induced invasion of breast cancer cell lines. Proc Natl Acad Sci U S A. 2006;103:5454–9.PubMedCrossRefGoogle Scholar
  122. 122.
    Ripka S, Konig A, Buchholz M, Wagner M, Sipos B, Kloppel G, Downward J, Gress T, Michl P. WNT5A—target of CUTL1 and potent modulator of tumor cell migration and invasion in pancreatic cancer. Carcinogenesis. 2007;28:1178–87.PubMedCrossRefGoogle Scholar
  123. 123.
    Pilarsky C, Ammerpohl O, Sipos B, Dahl E, Hartmann A, Wellmann A, Braunschweig T, Lohr M, Jesenofsky R, Friess H, Wente MN, Kristiansen G, Jahnke B, Denz A, Ruckert F, Schackert HK, Kloppel G, Kalthoff H, Saeger HD, Grutzmann R. Activation of Wnt signalling in stroma from pancreatic cancer identified by gene expression profiling. J Cell Mol Med. 2008;12:2823–35.PubMedCrossRefGoogle Scholar
  124. 124.
    Dissanayake SK, Wade M, Johnson CE, O’Connell MP, Leotlela PD, French AD, Shah KV, Hewitt KJ, Rosenthal DT, Indig FE, Jiang Y, Nickoloff BJ, Taub DD, Trent JM, Moon RT, Bittner M, Weeraratna AT. The Wnt5A/protein kinase C pathway mediates motility in melanoma cells via the inhibition of metastasis suppressors and initiation of an epithelial to mesenchymal transition. J Biol Chem. 2007;282:17259–71.PubMedCrossRefGoogle Scholar
  125. 125.
    Dissanayake SK, Weeraratna AT. Detecting PKC phosphorylation as part of the Wnt/calcium pathway in cutaneous melanoma. Methods Mol Biol. 2008;468:157–72.PubMedCrossRefGoogle Scholar
  126. 126.
    Wang Q, Williamson M, Bott S, Brookman-Amissah N, Freeman A, Nariculam J, Hubank MJ, Ahmed A, Masters JR. Hypomethylation of WNT5A, CRIP1 and S100P in prostate cancer. Oncogene. 2007;26:6560–5.PubMedCrossRefGoogle Scholar
  127. 127.
    Behrens J. Control of beta-catenin signaling in tumor development. Ann N Y Acad Sci. 2000;910:21–33.PubMedCrossRefGoogle Scholar
  128. 128.
    Peifer M, Polakis P. Wnt signaling in oncogenesis and embryogenesis—a look outside the nucleus. Science. 2000;287:1606–9.PubMedCrossRefGoogle Scholar
  129. 129.
    Taipale J, Beachy PA. The Hedgehog and Wnt signalling pathways in cancer. Nature. 2001;411:349–54.PubMedCrossRefGoogle Scholar
  130. 130.
    Verras M, Sun Z. Roles and regulation of Wnt signaling and beta-catenin in prostate cancer. Cancer Lett. 2006;237:22–32.PubMedCrossRefGoogle Scholar
  131. 131.
    Reya T, Clevers H. Wnt signalling in stem cells and cancer. Nature. 2005;434:843–50.PubMedCrossRefGoogle Scholar
  132. 132.
    Clevers H. Wnt breakers in colon cancer. Cancer Cell. 2004;5:5–6.PubMedCrossRefGoogle Scholar
  133. 133.
    Vermeulen L, De Sousa E, van der Melo HM, Cameron K, de Jong JH, Borovski T, Tuynman JB, Todaro M, Merz C, Rodermond H, Sprick MR, Kemper K, Richel DJ, Stassi G, Medema JP. Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat Cell Biol. 2010;12:468–76.PubMedCrossRefGoogle Scholar
  134. 134.
    Chesire DR, Ewing CM, Gage WR, Isaacs WB. In vitro evidence for complex modes of nuclear beta-catenin signaling during prostate growth and tumorigenesis. Oncogene. 2002;21:2679–94.PubMedCrossRefGoogle Scholar
  135. 135.
    Barker N, Clevers H. Mining the Wnt pathway for cancer therapeutics. Nat Rev Drug Discov. 2006;5:997–1014.PubMedCrossRefGoogle Scholar
  136. 136.
    Dihlmann S, von Knebel DM. Wnt/beta-catenin-pathway as a molecular target for future anti-cancer therapeutics. Int J Cancer. 2005;113:515–24.PubMedCrossRefGoogle Scholar
  137. 137.
    Gritli-Linde A, Bei M, Maas R, Zhang XM, Linde A, McMahon AP. Shh signaling within the dental epithelium is necessary for cell proliferation, growth and polarization. Development. 2002;129:5323–37.PubMedCrossRefGoogle Scholar
  138. 138.
    Yang L, Xie G, Fan Q, Xie J. Activation of the hedgehog-signaling pathway in human cancer and the clinical implications. Oncogene. 2010;29:469–81.PubMedCrossRefGoogle Scholar
  139. 139.
    Varjosalo M, Taipale J. Hedgehog: functions and mechanisms. Genes Dev. 2008;22:2454–72.PubMedCrossRefGoogle Scholar
  140. 140.
    Medina V, Calvo MB, az-Prado S, Espada J. Hedgehog signalling as a target in cancer stem cells. Clin Transl Oncol. 2009;11:199–207.PubMedCrossRefGoogle Scholar
  141. 141.
    Anton Aparicio LM, Garcia CR, Cassinello EJ, Valladares AM, Reboredo LM, Diaz PS, Aparicio GG. Prostate cancer and Hedgehog signalling pathway. Clin Transl Oncol. 2007;9:420–8.PubMedCrossRefGoogle Scholar
  142. 142.
    Varnat F, Duquet A, Malerba M, Zbinden M, Mas C, Gervaz P, Altaba A. Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion. EMBO Mol Med. 2009;1:338–51.PubMedCrossRefGoogle Scholar
  143. 143.
    Choi SS, Omenetti A, Witek RP, Moylan CA, Syn WK, Jung Y, Yang L, Sudan DL, Sicklick JK, Michelotti GA, Rojkind M, Diehl AM. Hedgehog pathway activation and epithelial-to-mesenchymal transitions during myofibroblastic transformation of rat hepatic cells in culture and cirrhosis. Am J Physiol Gastrointest Liver Physiol. 2009;297:G1093–106.PubMedCrossRefGoogle Scholar
  144. 144.
    Isohata N, Aoyagi K, Mabuchi T, Daiko H, Fukaya M, Ohta H, Ogawa K, Yoshida T, Sasaki H. Hedgehog and epithelial–mesenchymal transition signaling in normal and malignant epithelial cells of the esophagus. Int J Cancer. 2009;125:1212–21.PubMedCrossRefGoogle Scholar
  145. 145.
    Ohta H, Aoyagi K, Fukaya M, Danjoh I, Ohta A, Isohata N, Saeki N, Taniguchi H, Sakamoto H, Shimoda T, Tani T, Yoshida T, Sasaki H. Cross talk between hedgehog and epithelial–mesenchymal transition pathways in gastric pit cells and in diffuse-type gastric cancers. Br J Cancer. 2009;100:389–98.PubMedCrossRefGoogle Scholar
  146. 146.
    Omenetti A, Porrello A, Jung Y, Yang L, Popov Y, Choi SS, Witek RP, Alpini G, Venter J, Vandongen HM, Syn WK, Baroni GS, Benedetti A, Schuppan D, Diehl AM. Hedgehog signaling regulates epithelial–mesenchymal transition during biliary fibrosis in rodents and humans. J Clin Invest. 2008;118:3331–42.PubMedGoogle Scholar
  147. 147.
    Martelli AM, Evangelisti C, Follo MY, Ramazzotti G, Fini M, Giardino R, Manzoli L, McCubrey JA, Cocco L. Targeting the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling network in cancer stem cells. Curr Med Chem. 2011;18:2715–26.PubMedCrossRefGoogle Scholar
  148. 148.
    Carracedo A, Pandolfi PP. The PTEN-PI3K pathway: of feedbacks and cross-talks. Oncogene. 2008;27:5527–41.PubMedCrossRefGoogle Scholar
  149. 149.
    Eyler CE, Foo WC, LaFiura KM, McLendon RE, Hjelmeland AB, Rich JN. Brain cancer stem cells display preferential sensitivity to Akt inhibition. Stem Cells. 2008;26:3027–36.PubMedCrossRefGoogle Scholar
  150. 150.
    Dubrovska A, Elliott J, Salamone RJ, Kim S, Aimone LJ, Walker JR, Watson J, Sauveur-Michel M, Garcia-Echeverria C, Cho CY, Reddy VA, Schultz PG. Combination therapy targeting both tumor-initiating and differentiated cell populations in prostate carcinoma. Clin Cancer Res. 2010;16:5692–702.PubMedCrossRefGoogle Scholar
  151. 151.
    Zhou J, Wulfkuhle J, Zhang H, Gu P, Yang Y, Deng J, Margolick JB, Liotta LA, Petricoin III E, Zhang Y. Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc Natl Acad Sci U S A. 2007;104:16158–63.PubMedCrossRefGoogle Scholar
  152. 152.
    Yasuda A, Sawai H, Takahashi H, Ochi N, Matsuo Y, Funahashi H, Sato M, Okada Y, Takeyama H, Manabe T. Stem cell factor/c-kit receptor signaling enhances the proliferation and invasion of colorectal cancer cells through the PI3K/Akt pathway. Dig Dis Sci. 2007;52:2292–300.PubMedCrossRefGoogle Scholar
  153. 153.
    Nautiyal J, Banerjee S, Kanwar SS, Yu Y, Patel BB, Sarkar FH, Majumdar AP. Curcumin enhances dasatinib-induced inhibition of growth and transformation of colon cancer cells. Int J Cancer. 2011;128:951–61.PubMedCrossRefGoogle Scholar
  154. 154.
    Lin L, Liu Y, Li H, Li PK, Fuchs J, Shibata H, Iwabuchi Y, Lin J. Targeting colon cancer stem cells using a new curcumin analogue, GO-Y030. Br J Cancer. 2011;105:212–20.PubMedCrossRefGoogle Scholar
  155. 155.
    Ryu MJ, Cho M, Song JY, Yun YS, Choi IW, Kim DE, Park BS, Oh S. Natural derivatives of curcumin attenuate the Wnt/beta-catenin pathway through down-regulation of the transcriptional coactivator p300. Biochem Biophys Res Commun. 2008;377:1304–8.PubMedCrossRefGoogle Scholar
  156. 156.
    Jaiswal AS, Marlow BP, Gupta N, Narayan S. beta-Catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells. Oncogene. 2002;21:8414–27.PubMedCrossRefGoogle Scholar
  157. 157.
    Zhang J, Du Y, Wu C, Ren X, Ti X, Shi J, Zhao F, Yin H. Curcumin promotes apoptosis in human lung adenocarcinoma cells through miR-186* signaling pathway. Oncol Rep. 2010;24:1217–23.PubMedGoogle Scholar
  158. 158.
    Mudduluru G, George-William JN, Muppala S, Asangani IA, Kumarswamy R, Nelson LD, Allgayer H. Curcumin regulates miR-21 expression and inhibits invasion and metastasis in colorectal cancer. Biosci Rep. 2011;31:185–97.PubMedCrossRefGoogle Scholar
  159. 159.
    Kakarala M, Brenner DE, Korkaya H, Cheng C, Tazi K, Ginestier C, Liu S, Dontu G, Wicha MS. Targeting breast stem cells with the cancer preventive compounds curcumin and piperine. Breast Cancer Res Treat. 2010;122:777–85.PubMedCrossRefGoogle Scholar
  160. 160.
    Prasad CP, Rath G, Mathur S, Bhatnagar D, Ralhan R. Potent growth suppressive activity of curcumin in human breast cancer cells: modulation of Wnt/beta-catenin signaling. Chem Biol Interact. 2009;181:263–71.PubMedCrossRefGoogle Scholar
  161. 161.
    Squires MS, Hudson EA, Howells L, Sale S, Houghton CE, Jones JL, Fox LH, Dickens M, Prigent SA, Manson MM. Relevance of mitogen activated protein kinase (MAPK) and phosphotidylinositol-3-kinase/protein kinase B (PI3K/PKB) pathways to induction of apoptosis by curcumin in breast cells. Biochem Pharmacol. 2003;65:361–76.PubMedCrossRefGoogle Scholar
  162. 162.
    Teiten MH, Gaascht F, Cronauer M, Henry E, Dicato M, Diederich M. Anti-proliferative potential of curcumin in androgen-dependent prostate cancer cells occurs through modulation of the Wingless signaling pathway. Int J Oncol. 2011;38:603–11.PubMedGoogle Scholar
  163. 163.
    Hsieh A, Kim HS, Lim SO, Yu DY, Jung G. Hepatitis B viral X protein interacts with tumor suppressor adenomatous polyposis coli to activate Wnt/beta-catenin signaling. Cancer Lett. 2011;300:162–72.PubMedCrossRefGoogle Scholar
  164. 164.
    Choi HY, Lim JE, Hong JH. Curcumin interrupts the interaction between the androgen receptor and Wnt/beta-catenin signaling pathway in LNCaP prostate cancer cells. Prostate Cancer Prostatic Dis. 2010;13:343–9.PubMedCrossRefGoogle Scholar
  165. 165.
    Wang Z, Zhang Y, Banerjee S, Li Y, Sarkar FH. Notch-1 down-regulation by curcumin is associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells. Cancer. 2006;106:2503–13.PubMedCrossRefGoogle Scholar
  166. 166.
    Sarkar FH, Li Y, Wang Z, Padhye S. Lesson learned from nature for the development of novel anti-cancer agents: implication of isoflavone, curcumin, and their synthetic analogs. Curr Pharm Des. 2010;16:1801–12.PubMedCrossRefGoogle Scholar
  167. 167.
    Padhye S, Yang H, Jamadar A, Cui QC, Chavan D, Dominiak K, McKinney J, Banerjee S, Dou QP, Sarkar FH. New difluoro Knoevenagel condensates of curcumin, their Schiff bases and copper complexes as proteasome inhibitors and apoptosis inducers in cancer cells. Pharm Res. 2009;26:1874–80.PubMedCrossRefGoogle Scholar
  168. 168.
    Padhye S, Banerjee S, Chavan D, Pandye S, Swamy KV, Ali S, Li J, Dou QP, Sarkar FH. Fluorocurcumins as cyclooxygenase-2 inhibitor: molecular docking, pharmacokinetics and tissue distribution in mice. Pharm Res. 2009;26:2438–45.PubMedCrossRefGoogle Scholar
  169. 169.
    Ali S, Ahmad A, Banerjee S, Padhye S, Dominiak K, Schaffert JM, Wang Z, Philip PA, Sarkar FH. Gemcitabine sensitivity can be induced in pancreatic cancer cells through modulation of miR-200 and miR-21 expression by curcumin or its analogue CDF. Cancer Res. 2010;70:3606–17.PubMedCrossRefGoogle Scholar
  170. 170.
    Bao B, Ali S, Banerjee S, Wang Z, Logna F, Azmi AS, Kong D, Ahmad A, Li Y, Padhye S, Sarkar FH. Curcumin analogue CDF inhibits pancreatic tumor growth by switching on suppressor microRNAs and attenuating EZH2 expression. Cancer Res. 2012;72:335–45.PubMedCrossRefGoogle Scholar
  171. 171.
    Zhang Y, Talalay P, Cho CG, Posner GH. A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc Natl Acad Sci U S A. 1992;89:2399–403.PubMedCrossRefGoogle Scholar
  172. 172.
    Verhoeven DT, Verhagen H, Goldbohm RA, van den Brandt PA, van Poppel G. A review of mechanisms underlying anticarcinogenicity by brassica vegetables. Chem Biol Interact. 1997;103:79–129.PubMedCrossRefGoogle Scholar
  173. 173.
    Zhang Y, Tang L, Gonzalez V. Selected isothiocyanates rapidly induce growth inhibition of cancer cells. Mol Cancer Ther. 2003;2:1045–52.PubMedGoogle Scholar
  174. 174.
    Cho SD, Li G, Hu H, Jiang C, Kang KS, Lee YS, Kim SH, Lu J. Involvement of c-Jun N-terminal kinase in G2/M arrest and caspase-mediated apoptosis induced by sulforaphane in DU145 prostate cancer cells. Nutr Cancer. 2005;52:213–24.PubMedCrossRefGoogle Scholar
  175. 175.
    Jackson SJ, Singletary KW. Sulforaphane inhibits human MCF-7 mammary cancer cell mitotic progression and tubulin polymerization. J Nutr. 2004;134:2229–36.PubMedGoogle Scholar
  176. 176.
    Kuroiwa Y, Nishikawa A, Kitamura Y, Kanki K, Ishii Y, Umemura T, Hirose M. Protective effects of benzyl isothiocyanate and sulforaphane but not resveratrol against initiation of pancreatic carcinogenesis in hamsters. Cancer Lett. 2006;241:275–80.PubMedCrossRefGoogle Scholar
  177. 177.
    Shen G, Xu C, Chen C, Hebbar V, Kong AN. p53-independent G1 cell cycle arrest of human colon carcinoma cells HT-29 by sulforaphane is associated with induction of p21CIP1 and inhibition of expression of cyclin D1. Cancer Chemother Pharmacol. 2006;57:317–27.PubMedCrossRefGoogle Scholar
  178. 178.
    Singh AV, Xiao D, Lew KL, Dhir R, Singh SV. Sulforaphane induces caspase-mediated apoptosis in cultured PC-3 human prostate cancer cells and retards growth of PC-3 xenografts in vivo. Carcinogenesis. 2004;25:83–90.PubMedCrossRefGoogle Scholar
  179. 179.
    Zanichelli F, Capasso S, Cipollaro M, Pagnotta E, Carteni M, Casale F, Iori R, Galderisi U. Dose-dependent effects of R-sulforaphane isothiocyanate on the biology of human mesenchymal stem cells, at dietary amounts, it promotes cell proliferation and reduces senescence and apoptosis, while at anti-cancer drug doses, it has a cytotoxic effect. Age (Dordr). 2012;34:281–93.CrossRefGoogle Scholar
  180. 180.
    Srivastava RK, Tang SN, Zhu W, Meeker D, Shankar S. Sulforaphane synergizes with quercetin to inhibit self-renewal capacity of pancreatic cancer stem cells. Front Biosci (Elite Ed). 2011;3:515–28.CrossRefGoogle Scholar
  181. 181.
    Zhou W, Kallifatidis G, Baumann B, Rausch V, Mattern J, Gladkich J, Giese N, Moldenhauer G, Wirth T, Buchler MW, Salnikov AV, Herr I. Dietary polyphenol quercetin targets pancreatic cancer stem cells. Int J Oncol. 2010;37:551–61.PubMedGoogle Scholar
  182. 182.
    Kallifatidis G, Labsch S, Rausch V, Mattern J, Gladkich J, Moldenhauer G, Buchler MW, Salnikov AV, Herr I. Sulforaphane increases drug-mediated cytotoxicity toward cancer stem-like cells of pancreas and prostate. Mol Ther. 2011;19:188–95.PubMedCrossRefGoogle Scholar
  183. 183.
    Rausch V, Liu L, Kallifatidis G, Baumann B, Mattern J, Gladkich J, Wirth T, Schemmer P, Buchler MW, Zoller M, Salnikov AV, Herr I. Synergistic activity of sorafenib and sulforaphane abolishes pancreatic cancer stem cell characteristics. Cancer Res. 2010;70:5004–13.PubMedCrossRefGoogle Scholar
  184. 184.
    Li Y, Zhang T, Korkaya H, Liu S, Lee HF, Newman B, Yu Y, Clouthier SG, Schwartz SJ, Wicha MS, Sun D. Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. Clin Cancer Res. 2010;16:2580–90.PubMedCrossRefGoogle Scholar
  185. 185.
    Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006;5:493–506.PubMedCrossRefGoogle Scholar
  186. 186.
    Ahmad A, Farhan AS, Singh S, Hadi SM. DNA breakage by resveratrol and Cu(II): reaction mechanism and bacteriophage inactivation. Cancer Lett. 2000;154:29–37.PubMedCrossRefGoogle Scholar
  187. 187.
    Shankar S, Nall D, Tang SN, Meeker D, Passarini J, Sharma J, Srivastava RK. Resveratrol inhibits pancreatic cancer stem cell characteristics in human and KrasG12D transgenic mice by inhibiting pluripotency maintaining factors and epithelial–mesenchymal transition. PLoS One. 2011;6:e16530.PubMedCrossRefGoogle Scholar
  188. 188.
    Pandey PR, Okuda H, Watabe M, Pai SK, Liu W, Kobayashi A, Xing F, Fukuda K, Hirota S, Sugai T, Wakabayashi G, Koeda K, Kashiwaba M, Suzuki K, Chiba T, Endo M, Fujioka T, Tanji S, Mo YY, Cao D, Wilber AC, Watabe K. Resveratrol suppresses growth of cancer stem-like cells by inhibiting fatty acid synthase. Breast Cancer Res Treat. 2011;130:387–98.PubMedCrossRefGoogle Scholar
  189. 189.
    Zhang W, Sviripa V, Kril LM, Chen X, Yu T, Shi J, Rychahou P, Evers BM, Watt DS, Liu C. Fluorinated N, N-dialkylaminostilbenes for Wnt pathway inhibition and colon cancer repression. J Med Chem. 2011;54:1288–97.PubMedCrossRefGoogle Scholar
  190. 190.
    Lampe JW, Nishino Y, Ray RM, Wu C, Li W, Lin MG, Gao DL, Hu Y, Shannon J, Stalsberg H, Porter PL, Frankenfeld CL, Wahala K, Thomas DB. Plasma isoflavones and fibrocystic breast conditions and breast cancer among women in Shanghai, China. Cancer Epidemiol Biomarkers Prev. 2007;16:2579–86.PubMedCrossRefGoogle Scholar
  191. 191.
    Adlercreutz H, Markkanen H, Watanabe S. Plasma concentrations of phyto-oestrogens in Japanese men. Lancet. 1993;342:1209–10.PubMedCrossRefGoogle Scholar
  192. 192.
    Mills PK, Beeson WL, Phillips RL, Fraser GE. Cohort study of diet, lifestyle, and prostate cancer in Adventist men. Cancer. 1989;64:598–604.PubMedCrossRefGoogle Scholar
  193. 193.
    Jacobsen BK, Knutsen SF, Fraser GE. Does high soy milk intake reduce prostate cancer incidence? The Adventist Health Study (United States). Cancer Causes Control. 1998;9:553–7.PubMedCrossRefGoogle Scholar
  194. 194.
    Banerjee S, Li Y, Wang Z, Sarkar FH. Multi-targeted therapy of cancer by genistein. Cancer Lett. 2008;269:226–42.PubMedCrossRefGoogle Scholar
  195. 195.
    Chen Y, Zaman MS, Deng G, Majid S, Saini S, Liu J, Tanaka Y, Dahiya R. MicroRNAs 221/222 and genistein-mediated regulation of ARHI tumor suppressor gene in prostate cancer. Cancer Prev Res (Phila). 2011;4:76–86.CrossRefGoogle Scholar
  196. 196.
    Khan N, Mukhtar H. Multitargeted therapy of cancer by green tea polyphenols. Cancer Lett. 2008;269:269–80.PubMedCrossRefGoogle Scholar
  197. 197.
    Liu L, Lai CQ, Nie L, Ordovas J, Band M, Moser L, Meydani M. The modulation of endothelial cell gene expression by green tea polyphenol-EGCG. Mol Nutr Food Res. 2008;52:1182–92.PubMedCrossRefGoogle Scholar
  198. 198.
    Kim J, Zhang X, Rieger-Christ KM, Summerhayes IC, Wazer DE, Paulson KE, Yee AS. Suppression of Wnt signaling by the green tea compound (−)-epigallocatechin 3-gallate (EGCG) in invasive breast cancer cells. Requirement of the transcriptional repressor HBP1. J Biol Chem. 2006;281:10865–75.PubMedCrossRefGoogle Scholar
  199. 199.
    Van Aller GS, Carson JD, Tang W, Peng H, Zhao L, Copeland RA, Tummino PJ, Luo L. Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor. Biochem Biophys Res Commun. 2011;406:194–9.PubMedCrossRefGoogle Scholar
  200. 200.
    Fix LN, Shah M, Efferth T, Farwell MA, Zhang B. MicroRNA expression profile of MCF-7 human breast cancer cells and the effect of green tea polyphenon-60. Cancer Genomics Proteomics. 2010;7:261–77.PubMedGoogle Scholar
  201. 201.
    Siddiqui IA, Asim M, Hafeez BB, Adhami VM, Tarapore RS, Mukhtar H. Green tea polyphenol EGCG blunts androgen receptor function in prostate cancer. FASEB J. 2011;25:1198–207.PubMedCrossRefGoogle Scholar

Copyright information

© Controlled Release Society 2012

Authors and Affiliations

  • Prasad Dandawate
    • 1
  • Subhash Padhye
    • 1
    • 2
  • Aamir Ahmad
    • 2
  • Fazlul H. Sarkar
    • 2
    • 3
  1. 1.ISTRA, Department of Chemistry, Abeda Inamdar Senior CollegeUniversity of PunePuneIndia
  2. 2.Department of Pathology, Barbara Ann Karmanos Cancer InstituteWayne State University School of MedicineDetroitUSA
  3. 3.Department of Oncology, Barbara Ann Karmanos Cancer InstituteWayne State University School of MedicineDetroitUSA

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