The activity of SN33638, an inhibitor of AKR1C3, on testosterone and 17β-estradiol production and function in castration-resistant prostate cancer and ER-positive breast cancer

Frontiers in Oncology

Volumn 4 JUN, Issue , 2014, Pages

  Yin, Yarong Diana ^a   Fu, Melissa ^a   Brooke, Darby G ^a   Heinrich, Daniel M ^a   Denny, William A ^a,b   Jamieson, Stephen M F ^a,b  

^a UNIVERSITY OF AUCKLAND   (New Zealand)

^b MAURICE WILKINS CENTRE FOR MOLECULAR BIODISCOVERY   (New Zealand)

Author keywords

17 estradiol; AKR1C3; Castration resistant prostate cancer; ER positive breast cancer; Prostate specific antigen; SN33638; Testosterone

Indexed keywords

ANDROSTENEDIONE; ANTINEOPLASTIC AGENT; ESTRADIOL; ESTRONE; MESSENGER RNA; PROSTAGLANDIN F2 ALPHA; PROSTATE SPECIFIC ANTIGEN; SN 33638; TESTOSTERONE; TESTOSTERONE 17BETA DEHYDROGENASE; UNCLASSIFIED DRUG;

ARTICLE; CASTRATION RESISTANT PROSTATE CANCER; CELL CULTURE; CELL PROLIFERATION; CONTROLLED STUDY; DOWN REGULATION; DRUG ACTIVITY; ENZYME LINKED IMMUNOSORBENT ASSAY; ESTROGEN RECEPTOR POSITIVE BREAST CANCER; GENE EXPRESSION; HUMAN; HUMAN CELL; PROTEIN EXPRESSION; TESTOSTERONE RELEASE; UPREGULATION; WESTERN BLOTTING;

EID: 84904660980     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2014.00159     Document Type: Article

References (57)

1. Ali S, Coombes RC. Endocrine-responsive breast cancer and strategies for combating resistance. Nat Rev Cancer (2002) 2:101-12. doi:10.1038/nrc721
2. Taplin ME, Ho SM. Clinical review 134: the endocrinology of prostate cancer. J Clin Endocrinol Metab (2001) 86:3467-77. doi:10.1210/jcem.86.8.7782
3. Locke JA, Guns ES, Lubik AA, Adomat HH, Hendy SC, Wood CA, et al. Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer. Cancer Res (2008) 68:6407-15. doi:10.1158/0008-5472.CAN-07-5997
4. Montgomery RB, Mostaghel EA, Vessella R, Hess DL, Kalhorn TF, Higano CS, et al. Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res (2008) 68:4447-54. doi:10.1158/0008-5472.CAN-08-0249
5. Sasano H, Miki Y, Nagasaki S, Suzuki T. In situ estrogen production and its regulation in human breast carcinoma: from endocrinology to intracrinology. Pathol Int (2009) 59:777-89. doi:10.1111/j.1440-1827.2009.02444.x
6. Cai C, Chen S, Ng P, Bubley GJ, Nelson PS, Mostaghel EA, et al. Intratumoral de novo steroid synthesis activates androgen receptor in castration-resistant prostate cancer and is upregulated by treatment with CYP17A1 inhibitors. Cancer Res (2011) 71:6503-13. doi:10.1158/0008-5472.CAN-11-0532
7. Dozmorov MG, Azzarello JT, Wren JD, Fung KM, Yang Q, Davis JS, et al. Elevated AKR1C3 expression promotes prostate cancer cell survival and prostate cell-mediated endothelial cell tube formation: implications for prostate cancer progression. BMC Cancer (2010) 10:672. doi:10.1186/1471-2407-10-672
8. Hofland J, van Weerden WM, Dits NF, Steenbergen J, van Leenders GJ, Jenster G, et al. Evidence of limited contributions for intratumoral steroidogenesis in prostate cancer. Cancer Res (2010) 70:1256-64. doi:10.1158/0008-5472.CAN-09-2092
9. Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM, et al. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res (2006) 66:2815-25. doi:10.1158/0008-5472.CAN-05-4000
10. Byrns MC, Duan L, Lee SH, Blair IA, Penning TM. Aldo-keto reductase 1C3 expression in MCF-7 cells reveals roles in steroid hormone and prostaglandin metabolism that may explain its over-expression in breast cancer. J Steroid Biochem Mol Biol (2010) 118:177-87. doi:10.1016/j.jsbmb.2009.12.009
11. Penning TM, Byrns MC. Steroid hormone transforming aldo-keto reductases and cancer. Ann N Y Acad Sci (2009) 1155:33-42. doi:10.1111/j.1749-6632.2009.03700.x
12. Penning TM, Burczynski ME, Jez JM, Hung CF, Lin HK, Ma H, et al. Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones. Biochem J (2000) 351:67-77. doi:10.1042/0264-6021:3510067
13. Chang KH, Li R, Papari-Zareei M, Watumull L, Zhao YD, Auchus RJ, et al. Dihydrotestosterone synthesis bypasses testosterone to drive castration-resistant prostate cancer. Proc Natl Acad Sci U S A (2011) 108:13728-33. doi:10.1073/pnas.1107898108
14. Auchus RJ. The backdoor pathway to dihydrotestosterone. Trends Endocrinol Metab (2004) 15:432-8. doi:10.1016/j.tem.2004.09.004
15. Pfeiffer MJ, Smit FP, Sedelaar JP, Schalken JA. Steroidogenic enzymes and stem cell markers are upregulated during androgen deprivation in prostate cancer. Mol Med (2011) 17:657-64. doi:10.2119/molmed.2010.00143
16. Yuan X, Balk SP. Mechanisms mediating androgen receptor reactivation after castration. Urol Oncol (2009) 27:36-41. doi:10.1016/j.urolonc.2008.03.021
17. Shibuya R, Suzuki T, Miki Y, Yoshida K, Moriya T, Ono K, et al. Intratumoral concentration of sex steroids and expression of sex steroid-producing enzymes in ductal carcinoma in situ of human breast. Endocr Relat Cancer (2008) 15:113-24. doi:10.1677/ERC-07-0092
18. Oduwole OO, Li Y, Isomaa VV, Mantyniemi A, Pulkka AE, Soini Y, et al. 17beta-hydroxysteroid dehydrogenase type 1 is an independent prognostic marker in breast cancer. Cancer Res (2004) 64:7604-9. doi:10.1158/0008-5472.CAN-04-0446
19. Jansson AK, Gunnarsson C, Cohen M, Sivik T, Stal O. 17beta-hydroxysteroid dehydrogenase 14 affects estradiol levels in breast cancer cells and is a prognostic marker in estrogen receptor-positive breast cancer. Cancer Res (2006) 66:11471-7. doi:10.1158/0008-5472.CAN-06-1448
20. 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. doi:10.1186/1471-2407-4-27
21. Ji Q, Aoyama C, Nien YD, Liu PI, Chen PK, Chang L, et al. Selective loss of AKR1C1 and AKR1C2 in breast cancer and their potential effect on progesterone signaling. Cancer Res (2004) 64:7610-7. doi:10.1158/0008-5472.CAN-04-1608
22. Matsuura K, Shiraishi H, Hara A, Sato K, Deyashiki Y, Ninomiya M, et al. Identification of a principal mRNA species for human 3alpha-hydroxysteroid dehydrogenase isoform (AKR1C3) that exhibits high prostaglandin D2 11-ketoreductase activity. J Biochem (1998) 124:940-6. doi:10.1093/oxfordjournals.jbchem.a022211
23. Suzuki-Yamamoto T, Nishizawa M, Fukui M, Okuda-Ashitaka E, Nakajima T, Ito S, et al. cDNA cloning, expression and characterization of human prostaglandin F synthase. FEBS Lett (1999) 462:335-40. doi:10.1016/S0014-5793(99)01551-3
24. Birtwistle J, Hayden RE, Khanim FL, Green RM, Pearce C, Davies NJ, et al. The aldo-keto reductase AKR1C3 contributes to 7,12-dimethylbenz(a)anthracene-3,4-dihydrodiol mediated oxidative DNA damage in myeloid cells: implications for leukemogenesis. Mutat Res (2009) 662:67-74. doi:10.1016/j.mrfmmm.2008.12.010
25. Desmond JC, Mountford JC, Drayson MT, Walker EA, Hewison M, Ride JP, et al. 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.
26. 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) 181:1-6. doi:10.1016/j.toxlet.2008.06.858
27. Skarydova L, Tomanova R, Havlikova L, Stambergova H, Solich P, Wsol V. Deeper insight into the reducing biotransformation of bupropion in the human liver. Drug Metab Pharmacokinet (2014) 29:177-84. doi:10.2133/dmpk.DMPK-13-RG-051
28. Figueroa JD, Malats N, Garcia-Closas M, Real FX, Silverman D, Kogevinas M, et al. Bladder cancer risk and genetic variation in AKR1C3 and other metabolizing genes. Carcinogenesis (2008) 29:1955-62. doi:10.1093/carcin/bgn163
29. 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. doi:10.1074/jbc.M112424200
30. Guise CP, Abbattista MR, Singleton RS, Holford SD, Connolly J, Dachs GU, et al. The bioreductive prodrug PR-104A is activated under aerobic conditions by human aldo-keto reductase 1C3. Cancer Res (2010) 70:1573-84. doi:10.1158/0008-5472.CAN-09-3237
31. Jamieson SM, Gu Y, Manesh DM, El-Hoss J, Jing D, MacKenzie KL, et al. A novel fluorometric assay for aldo-keto reductase 1C3 predicts metabolic activation of the nitrogen mustard prodrug PR-104A in human leukaemia cells. Biochem Pharmacol (2014) 88:36-45. doi:10.1016/j.bcp.2013.12.019
32. MacLeod AK, McMahon M, Plummer SM, Higgins LG, Penning TM, Igarashi K, et al. 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. doi:10.1093/carcin/bgp176
33. Penning TM, Steckelbroeck S, Bauman DR, Miller MW, Jin Y, Peehl DM, et al. Aldo-keto reductase (AKR) 1C3: role in prostate disease and the development of specific inhibitors. Mol Cell Endocrinol (2006) 248:182-91. doi:10.1016/j.mce.2005.12.009
34. Lin HK, Steckelbroeck S, Fung KM, Jones AN, Penning TM. Characterization of a monoclonal antibody for human aldo-keto reductase AKR1C3 (type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta-hydroxysteroid dehydrogenase); immunohistochemical detection in breast and prostate. Steroids (2004) 69:795-801. doi:10.1016/j.steroids.2004.09.014
35. Heinrich DM, Flanagan JU, Jamieson SM, Silva S, Rigoreau LJ, Trivier E, et al. Synthesis and structure-activity relationships for 1-(4-(piperidin-1-ylsulfonyl)phenyl)pyrrolidin-2-ones as novel non-carboxylate inhibitors of the aldo-keto reductase enzyme AKR1C3. Eur J Med Chem (2013) 62:738-44. doi:10.1016/j.ejmech.2013.01.047
36. Jamieson SM, Brooke DG, Heinrich D, Atwell GJ, Silva S, Hamilton EJ, et al. 3-(3,4-Dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acids: highly potent and selective inhibitors of the type 5 17-beta-hydroxysteroid dehydrogenase AKR1C3. J Med Chem (2012) 55:7746-58. doi:10.1021/jm3007867
37. Mitchell JA, Akarasereenont P, Thiemermann C, Flower RJ, Vane JR. Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. Proc Natl Acad Sci U S A (1993) 90:11693-7. doi:10.1073/pnas.90.24.11693
38. Higaki Y, Usami N, Shintani S, Ishikura S, El-Kabbani O, Hara A. Selective and potent inhibitors of human 20 alpha-hydroxysteroid dehydrogenase (AKR1C1) that metabolizes neurosteroids derived from progesterone. Chem Biol Interact (2003) 14(3-144):503-13. doi:10.1016/S0009-2797(02)00206-5
39. Keller PJ, Lin AF, Arendt LM, Klebba I, Jones AD, Rudnick JA, et al. Mapping the cellular and molecular heterogeneity of normal and malignant breast tissues and cultured cell lines. Breast Cancer Res (2010) 12:R87. doi:10.1186/bcr2755
40. van Bokhoven A, Varella-Garcia M, Korch C, Johannes WU, Smith EE, Miller HL, et al. Molecular characterization of human prostate carcinoma cell lines. Prostate (2003) 57:205-25. doi:10.1002/pros.10290
41. Foehrenbacher A, Patel K, Abbattista M, Guise CP, Secomb TW, Wilson WR, et al. The role of bystander effects in the antitumor activity of the hypoxia-activated prodrug PR-104. Front Oncol (2013) 3:263. doi:10.3389/fonc.2013.00263
42. Kensler TW, Wakabayashi N, Biswal S. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol (2007) 47:89-116. doi:10.1146/annurev.pharmtox.46.120604.141046
43. Liu Y, Kern JT, Walker JR, Johnson JA, Schultz PG, Luesch H. A genomic screen for activators of the antioxidant response element. Proc Natl Acad Sci U S A (2007) 104:5205-10. doi:10.1073/pnas.0700898104
44. Day JM, Foster PA, Tutill HJ, Parsons MF, Newman SP, Chander SK, et al. 17beta-hydroxysteroid dehydrogenase Type 1, and not Type 12, is a target for endocrine therapy of hormone-dependent breast cancer. Int J Cancer (2008) 122:1931-40. doi:10.1002/ijc.23350
45. Le Bail JC, Laroche T, Marre-Fournier F, Habrioux G. Aromatase and 17beta-hydroxysteroid dehydrogenase inhibition by flavonoids. Cancer Lett (1998) 133:101-6. doi:10.1016/s0304-3835(98)00211-0
46. Adeniji AO, Chen M, Penning TM. AKR1C3 as a target in castrate resistant prostate cancer. J Steroid Biochem Mol Biol (2013) 137:136-49. doi:10.1016/j.jsbmb.2013.05.012
47. Hamid AR, Pfeiffer MJ, Verhaegh GW, Schaafsma E, Brandt A, Sweep FC, et al. Aldo-keto reductase family 1 member C3 (AKR1C3) is a biomarker and therapeutic target for castration-resistant prostate cancer. Mol Med (2012) 18:1449-55. doi:10.2119/molmed.2012.00296
48. Mitsiades N, Sung CC, Schultz N, Danila DC, He B, Eedunuri VK, et al. Distinct patterns of dysregulated expression of enzymes involved in androgen synthesis and metabolism in metastatic prostate cancer tumors. Cancer Res (2012) 72:6142-52. doi:10.1158/0008-5472.CAN-12-1335
49. Hofland J, van Weerden WM, Steenbergen J, Dits NF, Jenster G, de Jong FH. Activin A stimulates AKR1C3 expression and growth in human prostate cancer. Endocrinology (2012) 153:5726-34. doi:10.1210/en.2011-2065
50. Yepuru M, Wu Z, Kulkarni A, Yin F, Barrett CM, Kim J, et al. Steroidogenic enzyme AKR1C3 is a novel androgen receptor-selective coactivator that promotes prostate cancer growth. Clin Cancer Res (2013) 19:5613-25. doi:10.1158/1078-0432.CCR-13-1151
51. Geissler WM, Davis DL, Wu L, Bradshaw KD, Patel S, Mendonca BB, et al. Male pseudohermaphroditism caused by mutations of testicular 17 beta-hydroxysteroid dehydrogenase 3. Nat Genet (1994) 7:34-9. doi:10.1038/ng0594-34
52. Puranen T, Poutanen M, Ghosh D, Vihko R, Vihko P. Origin of substrate specificity of human and rat 17beta-hydroxysteroid dehydrogenase type 1, using chimeric enzymes and site-directed substitutions. Endocrinology (1997) 138:3532-9. doi:10.1210/en.138.8.3532
53. Samson M, Labrie F, Luu-The V. Characterization of type 15 17b-hydroxysteroid dehydrogenase. Endocr Rev (2012) 33:SAT-534.
54. Lin D, Wyatt AW, Xue H, Wang Y, Dong X, Haegert A, et al. High fidelity patient-derived xenografts for accelerating prostate cancer discovery and drug development. Cancer Res (2014) 74:1272-83. doi:10.1158/0008-5472.CAN-13-2921-T
55. Velica P, Davies NJ, Rocha PP, Schrewe H, Ride JP, Bunce CM. Lack of functional and expression homology between human and mouse aldo-keto reductase 1C enzymes: implications for modelling human cancers. Mol Cancer (2009) 8:121. doi:10.1186/1476-4598-8-121
56. Ayan D, Maltais R, Roy J, Poirier D. A new nonestrogenic steroidal inhibitor of 17beta-hydroxysteroid dehydrogenase type I blocks the estrogen-dependent breast cancer tumor growth induced by estrone. Mol Cancer Ther (2012) 11:2096-104. doi:10.1158/1535-7163.MCT-12-0299
57. Laplante Y, Rancourt C, Poirier D. Relative involvement of three 17beta-hydroxysteroid dehydrogenases (types 1, 7 and 12) in the formation of estradiol in various breast cancer cell lines using selective inhibitors. Mol Cell Endocrinol (2009) 301:146-53. doi:10.1016/j.mce.2008.08.026