Aldo-Keto Reductases as New Therapeutic Targets for Colon Cancer Chemoresistance

  • Toshiyuki Matsunaga
  • Ossama El-Kabbani
  • Akira Hara
Chapter
Part of the Resistance to Targeted Anti-Cancer Therapeutics book series (RTACT, volume 1)

Abstract

The aldo-keto reductase (AKR) superfamily comprises NAD(P)(H)-dependent enzymes that catalyze the oxidoreduction of a variety of substrates, including prostaglandins, steroids, toxic aldehydes and drugs. Among members of this superfamily, AKR1B10, AKR1C1, AKR1C2 and/or AKR1C3 are overexpressed in several types of cancers. Out of the four AKRs, AKR1B10, AKR1C1 and AKR1C3 are also significantly up-regulated with acquisition of resistance to several anticancer drugs in colon cancer, although the up-regulated enzyme species differ among themselves depending on the drug types. Studies with cell-based experiments have proposed multiple mechanisms leading to the drug resistance through regulation of cell proliferation and detoxification of lipid-derived toxicants by the up-regulated enzymes. Thus, the three enzymes have been recognized not only as potential diagnostic and/or prognostic markers, but also as potential therapeutic targets for the prevention and treatment of the colon cancer chemoresistance. Recently, potent and selective inhibitors of AKR1B10, AKR1C1 and AKR1C3 have been reported, and experimentally used for reversal of the colon cancer chemoresistance. In this chapter, we describe the current literature focusing mainly on the expression profiles of the three AKRs in chemoresistance of colon cancer cells and availability of the inhibitors for overcoming the anticancer drug resistance.

Keywords

Aldo-keto reductase AKR1B10 AKR1C1 AKR1C3 Colon cancers Chemotherapy Chemoresistance Proliferation 

Abbreviations

AKR

Aldo-keto reductase

ARE

Antioxidant response element

BPSA

3-Bromo-5-phenylsalicylic acid

CDDP

Cisplatin

CPSA

3-Chloro-5-phenyl salicylic acid

DOX

Doxorubicin

EGF

Epidermal growth factor

FAL

Farnesal

FOH

Farnesol

GGAL

Geranylgeranial

GGOH

Geranylgeraniol

HAHE

3-(4-Hydroxy-2-methoxyphenyl)acrylic acid 3-(3-hydroxyphenyl)propyl ester

HNE

4-Hydroxy-2-nonenal

HSD

Hydroxysteroid dehydrogenase

HT29/CDDP

HT29 phenotype resistant to cisplatin

Keap1

Kelch-like ECH-associated protein 1

LOHP

Oxaliplatin

MAPK

Mitogen-activated protein kinase

MMC

Mitomycin C

NSAID

Non-steroidal anti-inflammatory agent

NFκB

Nuclear factor-κB

Nrf2

Nuclear factor-erythroid 2-related factor 2

ONE

4-Oxo-2-nonenal

PHPC

(Z)-2-(4-Methoxyphenylimino)-7-hydroxy-N-(pyridin-2-yl)-2H-chromene-3-carboxamide

PG

Prostaglandin

PPAR

Peroxisome proliferator-activated receptor

ROS

Reactive oxygen species

VEGF

Vascular endothelial growth factor

Notes

No Conflict Statement

No potential conflicts of interest were disclosed.

References

  1. 1.
    Pham NM, Mizoue T, Tanaka K, Tsuji I, Tamakoshi A, Matsuo K, Ito H, Wakai K, Nagata C, Sasazuki S, Inoue M, Tsugane S. Research group for the development and evaluation of cancer prevention strategies in Japan. Physical activity and colorectal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol. 2012;42:2–13.PubMedGoogle Scholar
  2. 2.
    Kim R, Yamaguchi Y, Toge T. Adjuvant therapy for colorectal carcinoma. Anticancer Res. 2002;22:2413–8.PubMedGoogle Scholar
  3. 3.
    Saltz LB. Adjuvant therapy for colon cancer. Surg Oncol Clin N Am. 2010;19:819–27.PubMedGoogle Scholar
  4. 4.
    Dietel M. Molecular mechanisms and possibilities of overcoming drug resistance in gastrointestinal tumors. Recent Results Cancer Res. 1996;142:89–101.PubMedGoogle Scholar
  5. 5.
    Modjtahedi H, Essapen S. Epidermal growth factor receptor inhibitors in cancer treatment: advances challenges and opportunities. Anticancer Drugs. 2009;20:851–5.PubMedGoogle Scholar
  6. 6.
    Ahmed FE. Molecular markers that predict response to colon cancer therapy. Expert Rev Mol Diagn. 2005;5:353–75.PubMedGoogle Scholar
  7. 7.
    Ogiso Y, Tomida A, Lei S, Omura S, Tsuruo T. Proteasome inhibition circumvents solid tumor resistance to topoisomerase II-directed drugs. Cancer Res. 2000;60:2429–34.PubMedGoogle Scholar
  8. 8.
    Van Geelen CM, de Vries EG, de Jong S. Lessons from TRAIL-resistance mechanisms in colorectal cancer cells: paving the road to patient-tailored therapy. Drug Resist Updat. 2004;7:345–58.PubMedGoogle Scholar
  9. 9.
    Todaro M, Perez Alea M, Scopelliti A, Medema JP, Stassi G. IL-4-mediated drug resistance in colon cancer stem cells. Cell Cycle. 2008;7:309–313.Google Scholar
  10. 10.
    Todaro M, Francipane MG, Medema JP, Stassi G. Colon cancer stem cells: promise of targeted therapy. Gastroenterology. 2010;138:2151–62.PubMedGoogle Scholar
  11. 11.
    Lehne G, De Angelis P, den Boer M, Rugstad HE. Growth inhibition, cytokinesis failure and apoptosis of multidrug-resistant leukemia cells after treatment with P-glycoprotein inhibitory agents. Leukemia. 1999;13:768–78.PubMedGoogle Scholar
  12. 12.
    Fracasso PM, Goldstein LJ, de Alwis DP, Rader JS, Arquette MA, Goodner SA, Wright LP, Fears CL, Gazak RJ, Andre VA, Burgess MF, Slapak CA, Schellens JH. Phase I study of docetaxel in combination with the P-glycoprotein inhibitor, zosuquidar, in resistant malignancies. Clin Cancer Res. 2004;10:7220–8.PubMedGoogle Scholar
  13. 13.
    Enrique AA, Gema PC, Jeronimo JC, Auxiliadora GE. Role of anti-EGFR target therapy in colorectal carcinoma. Front Biosci. 2012;4:12–22.Google Scholar
  14. 14.
    Ferrarotto R, Hoff PM. Antiangiogenic drugs for colorectal cancer: exploring new possibilities. Clin Colorectal Cancer. 2013;12:1–7.Google Scholar
  15. 15.
    Hochster HS. Opportunities for newer agents in combination with oxaliplatin. Semin Oncol. 2003;30:62–7.PubMedGoogle Scholar
  16. 16.
    Bauman DR, Steckelbroeck S, Penning TM. The roles of aldo-keto reductases in steroid hormone action. Drug News Perspect. 2004;17:563–78.PubMedGoogle Scholar
  17. 17.
    Jin Y, Penning TM. Aldo-keto reductases and bioactivation/detoxication. Annu Rev Pharmacol Toxicol. 2007;47:263–92.PubMedGoogle Scholar
  18. 18.
    Barski OA, Tipparaju SM, Bhatnagar A. The aldo-keto reductase superfamily and its role in drug metabolism and detoxification. Drug Metab Rev. 2008;40:553–624.PubMedGoogle Scholar
  19. 19.
    Penning TM, Byrns MC. Steroid hormone transforming aldo-keto reductases and cancer. Ann N Y Acad Sci. 2009;1155:33–42.PubMedGoogle Scholar
  20. 20.
    El-Kabbani O, Dhagat U, Hara A. Inhibitors of human 20α-hydroxysteroid dehydrogenase (AKR1C1). J Steroid Biochem Mol Biol. 2011;125:105–11.PubMedGoogle Scholar
  21. 21.
    Matsunaga T, Wada Y, Endo S, Soda M, El-Kabbani O, Hara A. Aldo-keto reductase 1B10 and its role in proliferation capacity of drug-resistant cancers. Front Pharmacol. 2012;3:5.PubMedGoogle Scholar
  22. 22.
    Rižner TL. Enzymes of the AKR1B and AKR1C subfamilies and uterine diseases. Front Pharmacol. 2012;3:34.PubMedGoogle Scholar
  23. 23.
    Selga E, Noé V, Ciudad CJ. Transcriptional regulation of aldo-keto reductase 1C1 in HT29 human colon cancer cells resistant to methotrexate: role in the cell cycle and apoptosis. Biochem Pharmacol. 2008;75:414–26.PubMedGoogle Scholar
  24. 24.
    Matsunaga T, Yamane Y, Iida K, Endo S, Banno Y, El-Kabbani O, Hara A. Involvement of the aldo-keto reductase, AKR1B10, in mitomycin-c resistance through reactive oxygen species-dependent mechanisms. Anticancer Drugs. 2011;22:402–8.PubMedGoogle Scholar
  25. 25.
    Matsunaga T, Hojo A, Yamane Y, Endo S, El-Kabbani O, Hara A. Pathophysiological roles of aldo-keto reductases (AKR1C1 and AKR1C3) in development of cisplatin resistance in human colon cancers. Chem Biol Interact; 2013;202:234–42.Google Scholar
  26. 26.
    Mekhail-Ishak K, Hudson N, Tsao MS, Batist G. Implications for therapy of drug-metabolizing enzymes in human colon cancer. Cancer Res. 1989;49:4866–9.PubMedGoogle Scholar
  27. 27.
    Lotz C, Kelleher DK, Gassner B, Gekle M, Vaupel P, Thews O. Role of the tumor microenvironment in the activity and expression of the P-glycoprotein in human colon carcinoma cells. Oncol Rep. 2007;17:239–44.PubMedGoogle Scholar
  28. 28.
    Ueda K, Pastan I, Gottesman MM. Isolation and sequence of the promoter region of the human multidrug-resistance (P-glycoprotein) gene. J Biol Chem. 1987;262:17432–6.PubMedGoogle Scholar
  29. 29.
    Thiebaut F, Tsuruo T, Hamada H, Gottesman MM, Pastan I, Willingham MC. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci USA. 1987;84:7735–8.PubMedGoogle Scholar
  30. 30.
    Cordon-Cardo C, O’Brien JP, Boccia J, Casals D, Bertino JR, Melamed MR. Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues. J Histochem Cytochem. 1990;38:1277–87.PubMedGoogle Scholar
  31. 31.
    Klappe K, Hinrichs JW, Kroesen BJ, Sietsma H, Kok JW. MRP1 and glucosylceramide are coordinately over expressed and enriched in rafts during multidrug resistance acquisition in colon cancer cells. Int J Cancer. 2004;110:511–22.PubMedGoogle Scholar
  32. 32.
    Liu YY, Gupta V, Patwardhan GA, Bhinge K, Zhao Y, Bao J, Mehendale H, Cabot MC, Li YT, Jazwinski SM. Glucosylceramide synthase upregulates MDR1 expression in the regulation of cancer drug resistance through cSrc and β-catenin signaling. Mol Cancer. 2010;9:145.PubMedGoogle Scholar
  33. 33.
    Mendelsohn J, Baselga J. Epidermal growth factor receptor targeting in cancer. Semin Oncol. 2006;33:369–85.PubMedGoogle Scholar
  34. 34.
    Huang SA, Lin PF, Fan D, Price JE, Trujillo JM, Chakrabarty S. Growth modulation by epidermal growth factor (EGF) in human colonic carcinoma cells: constitutive expression of the human EGF gene. J Cell Physiol. 1991;148:220–7.PubMedGoogle Scholar
  35. 35.
    Radinsky R, Risin S, Fan D, Dong Z, Bielenberg D, Bucana CD, Fidler IJ. Level and function of epidermal growth factor receptor predict the metastatic potential of human colon carcinoma cells. Clin Cancer Res. 1995;1:19–31.PubMedGoogle Scholar
  36. 36.
    Karnes WE Jr, Weller SG, Adjei PN, Kottke TJ, Glenn KS, Gores GJ, Kaufmann SH. Inhibition of epidermal growth factor receptor kinase induces protease-dependent apoptosis in human colon cancer cells. Gastroenterology. 1998;114:930–9.PubMedGoogle Scholar
  37. 37.
    Jones MK, Tomikawa M, Mohajer B, Tarnawski AS. Gastrointestinal mucosal regeneration: role of growth factors. Front Biosci. 1999;4:D303–9.PubMedGoogle Scholar
  38. 38.
    Vincenzi B, Santini D, Rabitti C, Coppola R, Beomonte Zobel B, Trodella L, Tonini G. Cetuximab and irinotecan as third-line therapy in advanced colorectal cancer patients: a single centre phase II trial. Br J Cancer. 2006;94:792–797.Google Scholar
  39. 39.
    Stoeltzing O, Liu W, Reinmuth N, Parikh A, Ahmad SA, Jung YD, Fan F, Ellis LM. Angiogenesis and antiangiogenic therapy of colon cancer liver metastasis. Ann Surg Oncol. 2003;10:722–33.PubMedGoogle Scholar
  40. 40.
    Braghiroli MI, Sabbaga J, Hoff PM. Bevacizumab: overview of the literature. Expert Rev Anticancer Ther. 2012;12:567–80.PubMedGoogle Scholar
  41. 41.
    Dallas NA, Xia L, Fan F, Gray MJ, Gaur P, van Buren G 2nd, Samuel S, Kim MP, Lim SJ, Ellis LM. Chemoresistant colorectal cancer cells, the cancer stem cell phenotype, and increased sensitivity to insulin-like growth factor-I receptor inhibition. Cancer Res. 2009;69:1951–1957.Google Scholar
  42. 42.
    Reggiani Bonetti L, Migaldi M, Caredda E, Boninsegna A, Ponz De Leon M, Di Gregorio C, Barresi V, Scannone D, Danese S, Cittadini A, Sgambato A. Increased expression of CD133 is a strong predictor of poor outcome in stage I colorectal cancer patients. Scand J Gastroenterol. 2012;47:1211–1217.Google Scholar
  43. 43.
    Todaro M, Alea MP, Di Stefano AB, Cammareri P, Vermeulen L, Iovino F, Tripodo C, Russo A, Gulotta G, Medema JP, Stassi G. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell. 2007;1:389–402.PubMedGoogle Scholar
  44. 44.
    Lakshman M, Subramaniam V, Rubenthiran U, Jothy S. CD44 promotes resistance to apoptosis in human colon cancer cells. Exp Mol Pathol. 2004;77:18–25.PubMedGoogle Scholar
  45. 45.
    Wang C, Xie J, Guo J, Manning HC, Gore JC, Guo N. Evaluation of CD44 and CD133 as cancer stem cell markers for colorectal cancer. Oncol Rep. 2012;28:1301–8.PubMedGoogle Scholar
  46. 46.
    Cory AH, Cory JG. Lactacystin, a proteasome inhibitor, potentiates the apoptotic effect of parthenolide, an inhibitor of NFκB activation, on drug-resistant mouse leukemia L1210 cells. Anticancer Res. 2002;22:3805–9.PubMedGoogle Scholar
  47. 47.
    Loeffler-Ragg J, Mueller D, Gamerith G, Auer T, Skvortsov S, Sarg B, Skvortsova I, Schmitz KJ, Martin HJ, Krugmann J, Alakus H, Maser E, Menzel J, Hilbe W, Lindner H, Schmid KW, Zwierzina H. Proteomic identification of aldo-keto reductase AKR1B10 induction after treatment of colorectal cancer cells with the proteasome inhibitor bortezomib. Mol Cancer Ther. 2009;8:1995–2006.PubMedGoogle Scholar
  48. 48.
    Ebert B, Kisiela M, Wsól V, Maser E. Proteasome inhibitors MG-132 and Bortezomib induce AKR1C1, AKR1C3, AKR1B1, and AKR1B10 in human colon cancer cell lines SW-480 and HT-29. Chem Biol Interact. 2011;191:239–49.PubMedGoogle Scholar
  49. 49.
    Mackay H, Hedley D, Major P, Townsley C, Mackenzie M, Vincent M, Degendorfer P, Tsao MS, Nicklee T, Birle D, Wright J, Siu L, Moore M, Oza A. A phase II trial with pharmacodynamic endpoints of the Proteasome inhibitor Bortezomib in patients with metastatic colorectal cancer. Clin Cancer Res. 2005;11:5526–33.PubMedGoogle Scholar
  50. 50.
    Boccadoro M, Morgan G, Cavenagh J. Preclinical evaluation of the proteasome inhibitor bortezomib in cancer therapy. Cancer Cell Int. 2005;5:18.PubMedGoogle Scholar
  51. 51.
    Pitts TM, Morrow M, Kaufman SA, Tentler JJ, Eckhardt SG. Vorinostat and Bortezomib exert synergistic antiproliferative and proapoptotic effects in colon cancer cell models. Mol Cancer Ther. 2009;8:342–9.PubMedGoogle Scholar
  52. 52.
    Iwata S, Yano S, Ito Y, Ushijima Y, Gotoh K, Kawada J, Fujiwara S, Sugimoto K, Isobe Y, Nishiyama Y, Kimura H. Bortezomib induces apoptosis in T lymphoma cells and natural killer lymphoma cells independent of Epstein–Barr virus infection. Int J Cancer. 2011;129:2263–73.PubMedGoogle Scholar
  53. 53.
    Kusumoto S, Sugiyama T, Ando K, Hosaka T, Ishida H, Shirai T, Yamaoka T, Okuda K, Hirose T, Ohnishi T, Inoue F, Kanome T, Kadofuku T, Saijo N, Adachii M, Ohmori T. Combination effect between bortezomib and tumor necrosis factor alpha on gefitinib-resistant non-small cell lung cancer cell lines. Anticancer Res. 2009;29:2315–22.PubMedGoogle Scholar
  54. 54.
    Yanaba K, Asano Y, Tada Y, Sugaya M, Kadono T, Sato S. Proteasome inhibitor bortezomib ameliorates intestinal injury in mice. PLoS One. 2012;7:e34587.PubMedGoogle Scholar
  55. 55.
    Cao D, Fan ST, Chung SS. Identification and characterization of a novel human aldose reductase-like gene. J Biol Chem. 1998;273:11429–35.PubMedGoogle Scholar
  56. 56.
    Hyndman DJ, Flynn TG. Sequence and expression levels in human tissues of a new member of the aldo-keto reductase family. Biochim Biophys Acta. 1998;1399:198–202.PubMedGoogle Scholar
  57. 57.
    Fukumoto S, Yamauchi N, Moriguchi H, Hippo Y, Watanabe A, Shibahara J, Taniguchi H, Ishikawa S, Ito H, Yamamoto S, Iwanari H, Hironaka M, Ishikawa Y, Niki T, Sohara Y, Kodama T, Nishimura M, Fukayama M, Dosaka-Akita H, Aburatani H. Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers’ non-small cell lung carcinomas. Clin Cancer Res. 2005;11:1776–85.PubMedGoogle Scholar
  58. 58.
    Nagaraj NS, Beckers S, Mensah JK, Waigel S, Vigneswaran N, Zacharias W. Cigarette smoke condensate induces cytochromes P450 and aldo-keto reductases in oral cancer cells. Toxicol Lett. 2006;165:182–94.PubMedGoogle Scholar
  59. 59.
    Pierrou S, Broberg P, O’Donnell RA, Pawłowski K, Virtala R, Lindqvist E, Richter A, Wilson SJ, Angco G, Möller S, Bergstrand H, Koopmann W, Wieslander E, Strömstedt PE, Holgate ST, Davies DE, Lund J, Djukanovic R. Expression of genes involved in oxidative stress responses in airway epithelial cells of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007;175:577–86.PubMedGoogle Scholar
  60. 60.
    Zhang L, Lee JJ, Tang H, Fan YH, Xiao L, Ren H, Kurie J, Morice RC, Hong WK, Mao L. Impact of smoking cessation on global gene expression in the bronchial epithelium of chronic smokers. Cancer Prev Res (Phila). 2008;1:112–8.Google Scholar
  61. 61.
    Penning TM, Lerman C. Genomics of smoking exposure and cessation: lessons for cancer prevention and treatment. Cancer Prev Res (Phila). 2008;1:80–3.Google Scholar
  62. 62.
    Wang R, Wang G, Ricard MJ, Ferris B, Strulovici-Barel Y, Salit J, Hackett NR, Gudas LJ, Crystal RG. Smoking-induced upregulation of AKR1B10 expression in the airway epithelium of healthy individuals. Chest. 2010;138:1402–10.PubMedGoogle Scholar
  63. 63.
    Woenckhaus M, Klein-Hitpass L, Grepmeier U, Merk J, Pfeifer M, Wild P, Bettstetter M, Wuensch P, Blaszyk H, Hartmann A, Hofstaedter F, Dietmaier W. Smoking and cancer-related gene expression in bronchial epithelium and non-small-cell lung cancers. J Pathol. 2006;210:192–204.PubMedGoogle Scholar
  64. 64.
    Kim B, Lee HJ, Choi HY, Shin Y, Nam S, Seo G, Son DS, Jo J, Kim J, Lee J, Kim J, Kim K, Lee S. Clinical validity of the lung cancer biomarkers identified by bioinformatics analysis of public expression data. Cancer Res. 2007;67:7431–8.PubMedGoogle Scholar
  65. 65.
    Li CP, Goto A, Watanabe A, Murata K, Ota S, Niki T, Aburatani H, Fukayama M. AKR1B10 in usual interstitial pneumonia: expression in squamous metaplasia in association with smoking and lung cancer. Pathol Res Pract. 2008;204:295–304.PubMedGoogle Scholar
  66. 66.
    Kang MW, Lee ES, Yoon SY, Jo J, Lee J, Kim HK, Choi YS, Kim K, Shim YM, Kim J, Kim H. AKR1B10 is associated with smoking and smoking-related non-small-cell lung cancer. J Int Med Res. 2011;39:78–85.PubMedGoogle Scholar
  67. 67.
    Heringlake S, Hofdmann M, Fiebeler A, Manns MP, Schmiegel W, Tannapfel A. Identification and expression analysis of the aldo-ketoreductase 1–B10 gene in primary malignant liver tumours. J Hepatol. 2010;52:220–7.PubMedGoogle Scholar
  68. 68.
    Schmitz KJ, Sotiropoulos GC, Baba HA, Schmid KW, Müller D, Paul A, Auer T, Gamerith G, Loeffler-Ragg J. AKR1B10 expression is associated with less aggressive hepatocellular carcinoma: a clinicopathological study of 168 cases. Liver Int. 2011;31:810–6.PubMedGoogle Scholar
  69. 69.
    Yoshitake H, Takahashi M, Ishikawa H, Nojima M, Iwanari H, Watanabe A, Aburatani H, Yoshida K, Ishi K, Takamori K, Ogawa H, Hamakubo T, Kodama T, Araki Y. Aldo-keto reductase family 1, member B10 in uterine carcinomas: a potential risk factor of recurrence after surgical therapy in cervical cancer. Int J Gynecol Cancer. 2007;17:1300–6.PubMedGoogle Scholar
  70. 70.
    Lee HJ, Nam KT, Park HS, Kim MA, Lafleur BJ, Aburatani H, Yang HK, Kim WH, Goldenring JR. Gene expression profiling of metaplastic lineages identifies CDH17 as a prognostic marker in early stage gastric cancer. Gastroenterology. 2010;139:213–25.PubMedGoogle Scholar
  71. 71.
    Breton J, Gage MC, Hay AW, Keen JN, Wild CP, Donnellan C, Findlay JB, Hardie LJ. Proteomic screening of a cell line model of esophageal carcinogenesis identifies cathepsin d and aldo-keto reductase 1C2 and 1B10 dysregulation in Barrett’s esophagus and esophageal adenocarcinoma. J Proteome Res. 2008;7:1953–62.PubMedGoogle Scholar
  72. 72.
    Palackal NT, Lee SH, Harvey RG, Blair IA, Penning TM. Activation of polycyclic aromatic hydrocarbon trans-dihydrodiol proximate carcinogens by human aldo-keto reductase (AKR1C) enzymes and their functional overexpression in human lung carcinoma (A549) cells. J Biol Chem. 2002;277:24799–808.PubMedGoogle Scholar
  73. 73.
    Wang HW, Lin CP, Chiu JH, Chow KC, Kuo KT, Lin CS, Wang LS. Reversal of inflammation-associated dihydrodiol dehydrogenases (AKR1C1 and AKR1C2) overexpression and drug resistance in nonsmall cell lung cancer cells by Wogonin and Chrysin. Int J Cancer. 2007;120:2019–27.PubMedGoogle Scholar
  74. 74.
    Rižner TL, Smuc T, Rupreht R, Sinkovec J, Penning TM. AKR1C1 and AKR1C3 may determine progesterone and estrogen ratios in endometrial cancer. Mol Cell Endocrinol. 2006;248:126–35.PubMedGoogle Scholar
  75. 75.
    Tai HL, Lin TS, Huang HH, Lin TY, Chou MC, Chiou SH, Chow KC. Overexpression of aldo-keto reductase 1C2 as a high-risk factor in bladder cancer. Oncol Rep. 2007;17:305–11.PubMedGoogle Scholar
  76. 76.
    Desmond JC, Mountford JC, Drayson MT, Walker EA, Hewison M, Ride JP, Luong QT, Hayden RE, Vanin EF, Bunce CM. The aldo-keto reductase AKR1C3 is a novel suppressor of cell differentiation that provides a plausible target for the non-cyclooxygenase-dependent antineoplastic actions of nonsteroidal anti-inflammatory drugs. Cancer Res. 2003;63:505–12.PubMedGoogle Scholar
  77. 77.
    Miller VL, Lin HK, Murugan P, Fan M, Penning TM, Brame LS, Yang Q, Fung KM. Aldo-keto reductase family 1 member C3 (AKR1C3) is expressed in adenocarcinoma and squamous cell carcinoma but not small cell carcinoma. Int J Clin Exp Pathol. 2012;5:278–89.PubMedGoogle Scholar
  78. 78.
    Martinez I, Wang J, Hobson KF, Ferris RL, Khan SA. Identification of differentially expressed genes in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas. Eur J Cancer. 2007;43:415–32.PubMedGoogle Scholar
  79. 79.
    Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM, Febbo PG, Balk SP. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res. 2006;66:2815–25.PubMedGoogle Scholar
  80. 80.
    Lewis MJ, Wiebe JP, Heathcote JG. Expression of progesterone metabolizing enzyme genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, SRD5A2) is altered in human breast carcinoma. BMC Cancer. 2004;4:27.PubMedGoogle Scholar
  81. 81.
    Lau A, Villeneuve NF, Sun Z, Wong PK, Zhang DD. Dual roles of Nrf2 in cancer. Pharmacol Res. 2008;58:262–70.PubMedGoogle Scholar
  82. 82.
    MacLeod AK, McMahon M, Plummer SM, Higgins LG, Penning TM, Igarashi K, Hayes JD. Characterization of the cancer chemopreventive NRF2-dependent gene battery in human keratinocytes: demonstration that the KEAP1-NRF2 pathway, and not the BACH1-NRF2 pathway, controls cytoprotection against electrophiles as well as redox-cycling compounds. Carcinogenesis. 2009;30:1571–80.PubMedGoogle Scholar
  83. 83.
    Nishinaka T, Miura T, Okumura M, Nakao F, Nakamura H, Terada T. Regulation of aldo-keto reductase AKR1B10 gene expression: involvement of transcription factor Nrf2. Chem Biol Interact. 2011;191:185–91.PubMedGoogle Scholar
  84. 84.
    De Vries HE, Witte M, Hondius D, Rozemuller AJ, Drukarch B, Hoozemans J, van Horssen J. Nrf2-induced antioxidant protection: a promising target to counteract ROS-mediated damage in neurodegenerative disease? Free Radic Biol Med. 2008;45:1375–83.PubMedGoogle Scholar
  85. 85.
    Levonen AL, Landar A, Ramachandran A, Ceaser EK, Dickinson DA, Zanoni G, Morrow JD, Darley-Usmar VM. Cellular mechanisms of redox cell signalling: role of cysteine modification in controlling antioxidant defences in response to electrophilic lipid oxidation products. Biochem J. 2004;378:373–82.PubMedGoogle Scholar
  86. 86.
    Ciaccio PJ, Stuart JE, Tew KD. Overproduction of a 37.5 kDa cytosolic protein structurally related to prostaglandin F synthase in ethacrynic acid-resistant human colon cells. Mol Pharmacol. 1993;43:845–53.PubMedGoogle Scholar
  87. 87.
    Ciaccio PJ, Jaiswal AK, Tew KD. Regulation of human dihydrodiol dehydrogenase by michael acceptor xenobiotics. J Biol Chem. 1994;269:15558–62.PubMedGoogle Scholar
  88. 88.
    Singh A, Misra V, Thimmulappa RK, Lee H, Ames S, Hoque MO, Herman JG, Baylin SB, Sidransky D, Gabrielson E, Brock MV, Biswal S. Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer. PLoS Med. 2006;3:e420.PubMedGoogle Scholar
  89. 89.
    Shibata T, Kokubu A, Gotoh M, Ojima H, Ohta T, Yamamoto M, Hirohashi S. Genetic alteration of Keap1 confers constitutive Nrf2 activation and resistance to chemotherapy in gallbladder cancer. Gastroenterology. 2008;135:1358–68.PubMedGoogle Scholar
  90. 90.
    Loignon M, Miao W, Hu L, Bier A, Bismar TA, Scrivens PJ, Mann K, Basik M, Bouchard A, Fiset PO, Batist Z, Batist G. Cul3 overexpression depletes Nrf2 in breast cancer and is associated with sensitivity to carcinogens, to oxidative stress, and to chemotherapy. Mol Cancer Ther. 2009;8:2432–40.PubMedGoogle Scholar
  91. 91.
    Tang XH, Gudas LJ. Retinoids, retinoic acid receptors, and cancer. Annu Rev Pathol. 2011;6:345–64.PubMedGoogle Scholar
  92. 92.
    Crosas B, Hyndman DJ, Gallego O, Martras S, Parés X, Flynn TG, Farrés J. Human aldose reductase and human small intestine aldose reductase are efficient retinal reductases: consequences for retinoid metabolism. Biochem J. 2003;373:973–9.PubMedGoogle Scholar
  93. 93.
    Gallego O, Ruiz FX, Ardèvol A, Domínguez M, Alvarez R, de Lera AR, Rovira C, Farrés J, Fita I, Parés X. Structural basis for the high all-trans-retinaldehyde reductase activity of the tumor marker AKR1B10. Proc Natl Acad Sci USA. 2007;104:20764–9.PubMedGoogle Scholar
  94. 94.
    Ruiz FX, Gallego O, Ardèvol A, Moro A, Domínguez M, Alvarez S, Alvarez R, de Lera AR, Rovira C, Fita I, Parés X, Farrés J. Aldo-keto reductases from the AKR1B subfamily: retinoid specificity and control of cellular retinoic acid levels. Chem Biol Interact. 2009;178:171–7.PubMedGoogle Scholar
  95. 95.
    Matsuura K, Shiraishi H, Hara A, Sato K, Deyashiki Y, Ninomiya M, Sakai S. Identification of a principal mRNA species for human 3α-hydroxysteroid dehydrogenase isoform (AKR1C3) that exhibits high prostaglandin D2 11-ketoreductase activity. J Biochem. 1998;124:940–6.PubMedGoogle Scholar
  96. 96.
    Suzuki-Yamamoto T, Nishizawa M, Fukui M, Okuda-Ashitaka E, Nakajima T, Ito S, Watanabe K. cDNA cloning, expression and characterization of human prostaglandin F synthase. FEBS Lett. 1999;462:335–40.PubMedGoogle Scholar
  97. 97.
    Adams JW, Sah VP, Henderson SA, Brown JH. Tyrosine kinase and c-Jun NH2-terminal kinase mediate hypertrophic responses to prostaglandin F in cultured neonatal rat ventricular myocytes. Circ Res. 1998;83:167–78.PubMedGoogle Scholar
  98. 98.
    Zaragoza DB, Wilson RR, Mitchell BF, Olson DM. The interleukin 1β-induced expression of human prostaglandin F receptor messenger RNA in human myometrial-derived ULTR cells requires the transcription factor NFκB. Biol Reprod. 2006;75:697–704.PubMedGoogle Scholar
  99. 99.
    Endo S, Matsunaga T, Ohta C, Soda M, Kanamori A, Kitade Y, Ohno S, Tajima K, El-Kabbani O, Hara A. Roles of rat and human aldo-keto reductases in metabolism of farnesol and geranylgeraniol. Chem Biol Interact. 2011;191:261–8.PubMedGoogle Scholar
  100. 100.
    Winter-Vann AM, Casey PJ. Post-prenylation-processing enzymes as new targets in oncogenesis. Nat Rev Cancer. 2005;5:405–12.PubMedGoogle Scholar
  101. 101.
    Soda M, Hu D, Endo S, Takemura M, Li J, Wada R, Ifuku S, Zhao HT, El-Kabbani O, Ohta S, Yamamura K, Toyooka N, Hara A, Matsunaga T. Design, synthesis and evaluation of caffeic acid phenethyl ester-based inhibitors targeting a selectivity pocket in the active site of human aldo-keto reductase 1B10. Eur J Med Chem. 2012;48:321–9.PubMedGoogle Scholar
  102. 102.
    Endo S, Matsunaga T, Kanamori A, Otsuji Y, Nagai H, Sundaram K, El-Kabbani O, Toyooka N, Ohta S, Hara A. Selective inhibition of human type-5 17β-hydroxysteroid dehydrogenase (AKR1C3) by baccharin, a component of Brazilian propolis. J Nat Prod. 2012;75:716–21.PubMedGoogle Scholar
  103. 103.
    Yan R, Zu X, Ma J, Liu Z, Adeyanju M, Cao D. Aldo-keto reductase family 1B10 gene silencing results in growth inhibition of colorectal cancer cells: implication for cancer intervention. Int J Cancer. 2007;121:2301–6.PubMedGoogle Scholar
  104. 104.
    Zu X, Yan R, Ma J, Liao D, Cao D. AKR1B10: a potential target for cancer therapy. Biosci Hypothesis. 2009;2:31–3.Google Scholar
  105. 105.
    Byrns MC, Mindnich R, Duan L, Penning TM. Overexpression of aldo-keto reductase 1C3 (AKR1C3) in LNCaP cells diverts androgen metabolism towards testosterone resulting in resistance to the 5α-reductase inhibitor finasteride. J Steroid Biochem Mol Biol. 2012;130:7–15.PubMedGoogle Scholar
  106. 106.
    Ma J, Yan R, Zu X, Cheng JM, Rao K, Liao DF, Cao D. Aldo-keto reductase family 1B10 affects fatty acid synthesis by regulating the stability of acetyl-CoA carboxylase-α in breast cancer cells. J Biol Chem. 2008;283:3418–23.PubMedGoogle Scholar
  107. 107.
    Wang C, Yan R, Luo D, Watabe K, Liao DF, Cao D. Aldo-keto reductase family 1 member B10 promotes cell survival by regulating lipid synthesis and eliminating carbonyls. J Biol Chem. 2009;284:26742–8.PubMedGoogle Scholar
  108. 108.
    Lesgards JF, Gauthier C, Iovanna J, Vidal N, Dolla A, Stocker P. Effect of reactive oxygen and carbonyl species on crucial cellular antioxidant enzymes. Chem Biol Interact. 2011;190:28–34.PubMedGoogle Scholar
  109. 109.
    Burczynski ME, Sridhar GR, Palackal NT, Penning TM. The reactive oxygen species- and michael acceptor-inducible human aldo-keto reductase AKR1C1 reduces the α, β-unsaturated aldehyde 4-hydroxy-2-nonenal to 1,4-dihydroxy-2-nonene. J Biol Chem. 2001;276:2890–7.PubMedGoogle Scholar
  110. 110.
    Martin HJ, Maser E. Role of human aldo-keto-reductase AKR1B10 in the protection against toxic aldehydes. Chem Biol Interact. 2009;178:145–50.PubMedGoogle Scholar
  111. 111.
    Shen Y, Zhong L, Johnson S, Cao D. Human aldo-keto reductases 1B1 and 1B10: a comparative study on their enzyme activity toward electrophilic carbonyl compounds. Chem Biol Interact. 2011;191:192–8.PubMedGoogle Scholar
  112. 112.
    Hartley DP, Ruth JA, Petersen DR. The hepatocellular metabolism of 4-hydroxynonenal by alcohol dehydrogenase, aldehyde dehydrogenase, and glutathione S-transferase. Arch Biochem Biophys. 1995;316:197–205.PubMedGoogle Scholar
  113. 113.
    Martin HJ, Breyer-Pfaff U, Wsol V, Venz S, Block S, Maser E. Purification and characterization of AKR1B10 from human liver: role in carbonyl reduction of xenobiotics. Drug Metab Dispos. 2006;34:464–70.PubMedGoogle Scholar
  114. 114.
    Novotna R, Wsol V, Xiong G, Maser E. Inactivation of the anticancer drugs doxorubicin and oracin by aldo-keto reductase (AKR) 1C3. Toxicol Lett. 2008;181(1):1–6.PubMedGoogle Scholar
  115. 115.
    Kassner N, Huse K, Martin HJ, Gödtel-Armbrust U, Metzger A, Meineke I, Brockmöller J, Klein K, Zanger UM, Maser E, Wojnowski L. Carbonyl reductase 1 is a predominant doxorubicin reductase in the human liver. Drug Metab Dispos. 2008;36:2113–20.PubMedGoogle Scholar
  116. 116.
    Balendiran GK. Fibrates in the chemical action of daunorubicin. Curr Cancer Drug Targets. 2009;9:366–9.PubMedGoogle Scholar
  117. 117.
    Balendiran GK, Martin HJ, El-Hawari Y, Maser E. Cancer biomarker AKR1B10 and carbonyl metabolism. Chem Biol Interact. 2009;178:134–7.PubMedGoogle Scholar
  118. 118.
    Bains OS, Grigliatti TA, Reid RE, Riggs KW. Naturally occurring variants of human aldo-keto reductases with reduced in vitro metabolism of daunorubicin and doxorubicin. J Pharmacol Exp Ther. 2010;335:533–45.PubMedGoogle Scholar
  119. 119.
    Zhong L, Shen H, Huang C, Jing H, Cao D. AKR1B10 induces cell resistance to daunorubicin and idarubicin by reducing C13 ketonic group. Toxicol Appl Pharmacol. 2011;255:40–7.PubMedGoogle Scholar
  120. 120.
    Matsunaga T, Endo S, Takemura M, Soda M, Yamamura K, Tajima K, Miura T, Terada T, El-Kabbani O, Hara A. Reduction of cytotoxic p-quinone metabolites of tert-butylhydroquinone by human aldo-keto reductase (AKR) 1B10. Drug Metab Pharmacokinet. 2012;27:553–8.PubMedGoogle Scholar
  121. 121.
    Byrns MC, Jin Y, Penning TM. Inhibitors of type 5 17β-hydroxysteroid dehydrogenase (AKR1C3): overview and structural insights. J Steroid Biochem Mol Biol. 2011;125:95–104.PubMedGoogle Scholar
  122. 122.
    Brožič P, Turk S, Rižner TL, Gobec S. Inhibitors of aldo-keto reductases AKR1C1-AKR1C4. Curr Med Chem. 2011;18:2554–65.PubMedGoogle Scholar
  123. 123.
    Soda M, Endo S, Matsunaga T, Zhao HT, El-Kabbani O, Iinuma M, Yamamura K, Hara A. Inhibition of human aldose reductase-like protein (AKR1B10) by α- and γ-mangostins, major components of pericarps of mangosteen. Biol Pharm Bull. 2012;35:2075–80.Google Scholar
  124. 124.
    Matsunaga T, Endo S, Soda M, Zhao HT, El-Kabbani O, Tajima K, Hara A. Potent and selective inhibition of the tumor marker AKR1B10 by bisdemethoxycurcumin: probing the active site of the enzyme with molecular modeling and site-directed mutagenesis. Biochem Biophys Res Commun. 2009;389:128–32.PubMedGoogle Scholar
  125. 125.
    Takemura M, Endo S, Matsunaga T, Soda M, Zhao HT, El-Kabbani O, Tajima K, Iinuma M, Hara A. Selective inhibition of the tumor marker aldo-keto reductase family member 1B10 by oleanolic acid. J Nat Prod. 2011;74:1201–6.PubMedGoogle Scholar
  126. 126.
    Endo S, Matsunaga T, Kuwata K, Zhao HT, El-Kabbani O, Kitade Y, Hara A. Chromene-3-carboxamide derivatives discovered from virtual screening as potent inhibitors of the tumour maker, AKR1B10. Bioorg Med Chem. 2010;18:2485–90.PubMedGoogle Scholar
  127. 127.
    Zhao HT, Soda M, Endo S, Hara A, El-Kabbani O. Selectivity determinants of inhibitor binding to the tumour marker human aldose reductase-like protein (AKR1B10) discovered from molecular docking and database screening. Eur J Med Chem. 2010;45:4354–7.PubMedGoogle Scholar
  128. 128.
    Endo S, Matsunaga T, Mamiya H, Ohta C, Soda M, Kitade Y, Tajima K, Zhao HT, El-Kabbani O, Hara A. Kinetic studies of AKR1B10, human aldose reductase-like protein: endogenous substrates and inhibition by steroids. Arch Biochem Biophys. 2009;487:1–9.PubMedGoogle Scholar
  129. 129.
    Díez-Dacal B, Gayarre J, Gharbi S, Timms JF, Coderch C, Gago F, Pérez-Sala D. Identification of aldo-keto reductase AKR1B10 as a selective target for modification and inhibition by prostaglandin A(1): implications for antitumoral activity. Cancer Res. 2011;71:4161–71.PubMedGoogle Scholar
  130. 130.
    El-Kabbani O, Scammells PJ, Day T, Dhagat U, Endo S, Matsunaga T, Soda M, Hara A. Structure-Based optimization and biological evaluation of human 20α-hydroxysteroid dehydrogenase (AKR1C1) salicylic acid-based inhibitors. Eur J Med Chem. 2010;45:5309–17.PubMedGoogle Scholar
  131. 131.
    El-Kabbani O, Scammells PJ, Gosling J, Dhagat U, Endo S, Matsunaga T, Soda M, Hara A. Structure-guided design, synthesis, and evaluation of salicylic acid-based inhibitors targeting a selectivity pocket in the active site of human 20α-hydroxysteroid dehydrogenase (AKR1C1). J Med Chem. 2009;52:3259–64.PubMedGoogle Scholar
  132. 132.
    Dhagat U, Endo S, Sumii R, Hara A, El-Kabbani O. Selectivity determinants of inhibitor binding to human 20α-hydroxysteroid dehydrogenase: crystal structure of the enzyme in ternary complex with coenzyme and the potent inhibitor 3,5-dichlorosalicylic acid. J Med Chem. 2008;51:4844–8.PubMedGoogle Scholar
  133. 133.
    Higaki Y, Usami N, Shintani S, Ishikura S, El-Kabbani O, Hara A. Selective and potent inhibitors of human 20α-hydroxysteroid dehydrogenase (AKR1C1) that metabolizes neurosteroids derived from progesterone. Chem Biol Interact. 2003;143–144:503–13.PubMedGoogle Scholar
  134. 134.
    Brozic P, Smuc T, Gobec S, Rizner TL. Phytoestrogens as inhibitors of the human progesterone metabolizing enzyme AKR1C1. Mol Cell Endocrinol. 2006;259:30–42.PubMedGoogle Scholar
  135. 135.
    Skarydová L, Zivná L, Xiong G, Maser E, Wsól V. AKR1C3 as a potential target for the inhibitory effect of dietary flavonoids. Chem Biol Interact. 2009;178:138–44.PubMedGoogle Scholar
  136. 136.
    Byrns MC, Steckelbroeck S, Penning TM. An indomethacin analogue, N-(4-chlorobenzoyl)-melatonin, is a selective inhibitor of aldo-keto reductase 1C3 (type 2 3α-HSD, type 5 17β-HSD, and prostaglandin F synthase), a potential target for the treatment of hormone dependent and hormone independent malignancies. Biochem Pharmacol. 2008;75:484–93.PubMedGoogle Scholar
  137. 137.
    Adeniji AO, Twenter BM, Byrns MC, Jin Y, Chen M, Winkler JD, Penning TM. Development of potent and selective inhibitors of aldo-keto reductase 1C3 (Type 5 17β-hydroxysteroid dehydrogenase) based on N-phenyl-aminobenzoates and their structure-activity relationships. J Med Chem. 2012;55:2311–23.PubMedGoogle Scholar
  138. 138.
    Jamieson SM, Brooke DG, Heinrich D, Atwell GJ, Silva S, Hamilton EJ, Turnbull AP, Rigoreau LJ, Trivier E, Soudy C, Samlal SS, Owen PJ, Schroeder E, Raynham T, Flanagan JU, Denny WA. 3-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acids: highly potent and selective inhibitors of the type 5 17β-hydroxysteroid dehydrogenase AKR1C3. J Med Chem. 2012;55:7746–58.PubMedGoogle Scholar
  139. 139.
    Brožič P, Turk S, Adeniji AO, Konc J, Janežič D, Penning TM. Lanišnik Rižner T, Gobec S. Selective inhibitors of aldo-keto reductases AKR1C1 and AKR1C3 discovered by virtual screening of a fragment library. J Med Chem. 2012;55:7417–24.PubMedGoogle Scholar
  140. 140.
    Matsunaga T, Hosogai M, Arakaki M, Endo S, El-Kabbani O, Hara A. 9,10-Phenanthrenequinone induces monocytic differentiation of U937 cells through regulating expression of aldo-keto reductase 1C3. Biol Pharm Bull. 2012;35:1598–602.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Toshiyuki Matsunaga
    • 1
  • Ossama El-Kabbani
    • 2
  • Akira Hara
    • 1
  1. 1.Laboratory of BiochemistryGifu Pharmaceutical UniversityGifuJapan
  2. 2.Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleAustralia

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