Antiprogestin mifepristone inhibits the growth of cancer cells of reproductive and non-reproductive origin regardless of progesterone receptor expression

BMC Cancer

Volumn 11, Issue , 2011, Pages

  Tieszen, Chelsea R ^a   Goyeneche, Alicia A ^a   Brandhagen, BreeAnn N ^a   Ortbahn, Casey T ^a   Telleria, Carlos M ^a  

^a UNIVERSITY OF SOUTH DAKOTA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIN DEPENDENT KINASE 2; HISTONE H1; MIFEPRISTONE; PROGESTERONE RECEPTOR; ANDROGEN RECEPTOR; CYTOSTATIC AGENT; ESTROGEN RECEPTOR;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BONE CANCER; BREAST CANCER; CANCER CELL CULTURE; CANCER INHIBITION; CELL COUNT; CELL CYCLE ARREST; CELL CYCLE G1 PHASE; CELL CYCLE S PHASE; CELL DEATH; CELL STRAIN MCF 7; CONCENTRATION RESPONSE; CONTROLLED STUDY; DNA CONTENT; DRUG CYTOTOXICITY; DRUG EFFICACY; ENZYME ACTIVITY; FEMALE; HORMONE RESPONSE; HUMAN; HUMAN CELL; MALE; NERVOUS SYSTEM TUMOR; OVARY CANCER; PROSTATE CANCER; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; WESTERN BLOTTING; CELL CYCLE; CELL PROLIFERATION; DRUG EFFECT; DRUG RESISTANCE; GENE EXPRESSION REGULATION; METABOLISM; NEOPLASM; PATHOPHYSIOLOGY; TUMOR CELL LINE;

CELL CYCLE; CELL LINE, TUMOR; CELL PROLIFERATION; CYTOSTATIC AGENTS; DRUG RESISTANCE, NEOPLASM; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MIFEPRISTONE; NEOPLASMS; RECEPTORS, ANDROGEN; RECEPTORS, ESTROGEN; RECEPTORS, PROGESTERONE;

EID: 79957475955     PISSN: None     EISSN: 14712407     Source Type: Journal    
DOI: 10.1186/1471-2407-11-207     Document Type: Article

References (65)

1. Benagiano G, Bastianelli C, Farris M. Selective progesterone receptor modulators 1: use during pregnancy. Expert Opin Pharmacother 2008, 9(14):2459-2472. 10.1517/14656566.9.14.2459, 18778184.
2. Benagiano G, Bastianelli C, Farris M. Selective progesterone receptor modulators 2: use in reproductive medicine. Expert Opin Pharmacother 2008, 9(14):2473-2485. 10.1517/14656566.9.14.2473, 18778185.
3. Moller C, Hoffmann J, Kirkland TA, Schwede W. Investigational developments for the treatment of progesterone-dependent diseases. Expert Opin Investig Drugs 2008, 17(4):469-479. 10.1517/13543784.17.4.469, 18363513.
4. Benagiano G, Bastianelli C, Farris M. Selective progesterone receptor modulators 3: use in oncology, endocrinology and psychiatry. Expert Opin Pharmacother 2008, 9(14):2487-2496. 10.1517/14656566.9.14.2487, 18778186.
5. Horwitz KB. The antiprogestin RU38 486: receptor-mediated progestin versus antiprogestin actions screened in estrogen-insensitive T47Dco human breast cancer cells. Endocrinology 1985, 116(6):2236-2245. 10.1210/endo-116-6-2236, 4039656.
6. Lin VC, Aw SE, Ng EH, Tan MG. Demonstration of mixed properties of RU486 in progesterone receptor (PR)-transfected MDA-MB-231 cells: a model for studying the functions of progesterone analogues. Br J Cancer 2001, 85(12):1978-1986. 10.1054/bjoc.2001.2167, 2364017, 11747343.
7. Liang Y, Hou M, Kallab AM, Barrett JT, El Etreby F, Schoenlein PV. Induction of antiproliferation and apoptosis in estrogen receptor negative MDA-231 human breast cancer cells by mifepristone and 4-hydroxytamoxifen combination therapy: a role for TGFbeta1. Int J Oncol 2003, 23(2):369-380.
8. El Etreby MF, Liang Y, Lewis RW. Induction of apoptosis by mifepristone and tamoxifen in human LNCaP prostate cancer cells in culture. Prostate 2000, 43(1):31-42. 10.1002/(SICI)1097-0045(20000401)43:1<31::AID-PROS5>3.0.CO;2-#, 10725863.
9. Moe BT, Vereide AB, Orbo A, Jaeger R, Sager G. Levonorgestrel, medroxyprogesterone and progesterone cause a concentration-dependent reduction in endometrial cancer (Ishikawa) cell density, and high concentrations of progesterone and mifepristone act in synergy. Anticancer Research 2009, 29(4):1047-1052.
10. Moe BG, Vereide AB, Orbo A, Sager G. High concentrations of progesterone and mifepristone mutually reinforce cell cycle retardation and induction of apoptosis. Anticancer Research 2009, 29(4):1053-1058.
11. Fjelldal R, Moe BT, Orbo A, Sager G. MCF-7 cell apoptosis and cell cycle arrest: non-genomic effects of progesterone and mifepristone (RU-486). Anticancer Research 2010, 30(12):4835-4840.
12. Lin MF, Kawachi MH, Stallcup MR, Grunberg SM, Lin FF. Growth inhibition of androgen-insensitive human prostate carcinoma cells by a 19-norsteroid derivative agent, mifepristone. Prostate 1995, 26(4):194-204. 10.1002/pros.2990260405, 7716084.
13. Goyeneche AA, Caron RW, Telleria CM. Mifepristone inhibits ovarian cancer cell growth in vitro and in vivo. Clin Cancer Res 2007, 13(11):3370-3379. 10.1158/1078-0432.CCR-07-0164, 2505183, 17545545.
14. Freeburg EM, Goyeneche AA, Seidel EE, Telleria CM. Resistance to cisplatin does not affect sensitivity of human ovarian cancer cell lines to mifepristone cytotoxicity. Cancer Cell Int 2009, 9:4. 10.1186/1475-2867-9-4, 2661041, 19222856.
15. Freeburg EM, Goyeneche AA, Telleria CM. Mifepristone abrogates repopulation of ovarian cancer cells in between courses of cisplatin treatment. Int J Oncol 2009, 34(3):743-755. 2690705, 19212679.
16. Fauvet R, Dufournet Etienne C, Poncelet C, Bringuier AF, Feldmann G, Darai E. Effects of progesterone and anti-progestin (mifepristone) treatment on proliferation and apoptosis of the human ovarian cancer cell line, OVCAR-3. Oncol Rep 2006, 15(4):743-748.
17. Rose FV, Barnea ER. Response of human ovarian carcinoma cell lines to antiprogestin mifepristone. Oncogene 1996, 12(5):999-1003.
18. Akahira J, Suzuki T, Ito K, Kaneko C, Darnel AD, Moriya T, Okamura K, Yaegashi N, Sasano H. Differential expression of progesterone receptor isoforms A and B in the normal ovary, and in benign, borderline, and malignant ovarian tumors. Jpn J Cancer Res 2002, 93(7):807-815.
19. Hamilton TC, Behrens BC, Louie KG, Ozols RF. Induction of progesterone receptor with 17 beta-estradiol in human ovarian cancer. J Clin Endocrinol Metab 1984, 59(3):561-563. 10.1210/jcem-59-3-561, 6746867.
20. Keith Bechtel M, Bonavida B. Inhibitory effects of 17beta-estradiol and progesterone on ovarian carcinoma cell proliferation: a potential role for inducible nitric oxide synthase. Gynecol Oncol 2001, 82(1):127-138. 10.1006/gyno.2001.6221, 11426974.
21. McDonnel AC, Murdoch WJ. High-dose progesterone inhibition of urokinase secretion and invasive activity by SKOV-3 ovarian carcinoma cells: evidence for a receptor-independent nongenomic effect on the plasma membrane. J Steroid Biochem Mol Biol 2001, 78(2):185-191. 10.1016/S0960-0760(01)00081-4, 11566443.
22. Charles NJ, Thomas P, Lange CA. Expression of membrane progesterone receptors (mPR/PAQR) in ovarian cancer cells: implications for progesterone-induced signaling events. Horm Canc 2010, 1(4):167-176.
23. Peluso JJ, Gawkowska A, Liu X, Shioda T, Pru JK. Progesterone receptor membrane component-1 regulates the development and Cisplatin sensitivity of human ovarian tumors in athymic nude mice. Endocrinology 2009, 150(11):4846-4854. 10.1210/en.2009-0730, 19797399.
24. Vermeulen K, Van Bockstaele DR, Berneman ZN. The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif 2003, 36(3):131-149. 10.1046/j.1365-2184.2003.00266.x, 12814430.
25. Mahajan DK, London SN. Mifepristone (RU486): a review. Fertil Steril 1997, 68(6):967-976. 10.1016/S0015-0282(97)00189-1, 9418681.
26. Schneider CC, Gibb RK, Taylor DD, Wan T, Gercel-Taylor C. Inhibition of endometrial cancer cell lines by mifepristone (RU 486). J Soc Gynecol Investig 1998, 5(6):334-338. 10.1016/S1071-5576(98)00037-9, 9824816.
27. Pinski J, Halmos G, Shirahige Y, Wittliff JL, Schally AV. Inhibition of growth of the human malignant glioma cell line (U87MG) by the steroid hormone antagonist RU486. J Clin Endocrinol Metab 1993, 77(5):1388-1392. 10.1210/jc.77.5.1388, 8077338.
28. Lee WH. Characterization of a newly established malignant meningioma cell line of the human brain: IOMM-Lee. Neurosurgery 1990, 27(3):389-395. discussion 396, 10.1227/00006123-199009000-00008, 2234331.
29. Wahab M, Al-Azzawi F. Meningioma and hormonal influences. Climacteric 2003, 6(4):285-292.
30. Grunberg SM, Weiss MH, Russell CA, Spitz IM, Ahmadi J, Sadun A, Sitruk-Ware R. Long-term administration of mifepristone (RU486): clinical tolerance during extended treatment of meningioma. Cancer Invest 2006, 24(8):727-733. 10.1080/07357900601062339, 17162554.
31. Spitz IM, Grunberg SM, Chabbert-Buffet N, Lindenberg T, Gelber H, Sitruk-Ware R. Management of patients receiving long-term treatment with mifepristone. Fertil Steril 2005, 84(6):1719-1726. 10.1016/j.fertnstert.2005.05.056, 16359971.
32. Petz LN, Ziegler YS, Loven MA, Nardulli AM. Estrogen receptor alpha and activating protein-1 mediate estrogen responsiveness of the progesterone receptor gene in MCF-7 breast cancer cells. Endocrinology 2002, 143(12):4583-4591. 10.1210/en.2002-220369, 12446585.
33. Horwitz KB, Aiginger P, Kuttenn F, McGuire WL. Nuclear estrogen receptor release from antiestrogen suppression: amplified induction of progesterone receptor in MCF-7 human breast cancer cells. Endocrinology 1981, 108(5):1703-1709. 10.1210/endo-108-5-1703, 7194178.
34. Vienonen A, Syvala H, Miettinen S, Tuohimaa P, Ylikomi T. Expression of progesterone receptor isoforms A and B is differentially regulated by estrogen in different breast cancer cell lines. J Steroid Biochem Mol Biol 2002, 80(3):307-313. 10.1016/S0960-0760(02)00027-4, 11948015.
35. Thomas M, Monet JD. Combined effects of RU486 and tamoxifen on the growth and cell cycle phases of the MCF-7 cell line. J Clin Endocrinol Metab 1992, 75(3):865-870. 10.1210/jc.75.3.865, 1517379.
36. El Etreby MF, Liang Y, Wrenn RW, Schoenlein PV. Additive effect of mifepristone and tamoxifen on apoptotic pathways in MCF-7 human breast cancer cells. Breast Cancer Res Treat 1998, 51(2):149-168. 10.1023/A:1006078032287, 9879777.
37. Gaddy VT, Barrett JT, Delk JN, Kallab AM, Porter AG, Schoenlein PV. Mifepristone induces growth arrest, caspase activation, and apoptosis of estrogen receptor-expressing, antiestrogen-resistant breast cancer cells. Clin Cancer Res 2004, 10(15):5215-5225. 10.1158/1078-0432.CCR-03-0637, 15297425.
38. Darro F, Cahen P, Vianna A, Decaestecker C, Nogaret JM, Leblond B, Chaboteaux C, Ramos C, Petein M, Budel V, Schoofs A, Pourrias B, Kiss R. Growth inhibition of human in vitro and mouse in vitro and in vivo mammary tumor models by retinoids in comparison with tamoxifen and the RU-486 anti-progestagen. Breast Cancer Res Treat 1998, 51(1):39-55. 10.1023/A:1006098124087, 9877028.
39. El Etreby MF, Liang Y, Johnson MH, Lewis RW. Antitumor activity of mifepristone in the human LNCaP, LNCaP-C4, and LNCaP-C4-2 prostate cancer models in nude mice. Prostate 2000, 42(2):99-106. 10.1002/(SICI)1097-0045(20000201)42:2<99::AID-PROS3>3.0.CO;2-I, 10617866.
40. Bonkhoff H, Fixemer T, Hunsicker I, Remberger K. Progesterone receptor expression in human prostate cancer: correlation with tumor progression. Prostate 2001, 48(4):285-291. 10.1002/pros.1108, 11536308.
41. Sasaki M, Tanaka Y, Perinchery G, Dharia A, Kotcherguina I, Fujimoto S, Dahiya R. Methylation and inactivation of estrogen, progesterone, and androgen receptors in prostate cancer. J Natl Cancer Inst 2002, 94(5):384-390.
42. Agoulnik IU, Krause WC, Bingman WE, Rahman HT, Amrikachi M, Ayala GE, Weigel NL. Repressors of androgen and progesterone receptor action. J Biol Chem 2003, 278(33):31136-31148. 10.1074/jbc.M305153200, 12771131.
43. Rogatsky I, Hittelman AB, Pearce D, Garabedian MJ. Distinct glucocorticoid receptor transcriptional regulatory surfaces mediate the cytotoxic and cytostatic effects of glucocorticoids. Mol Cell Biol 1999, 19(7):5036-5049. 84339, 10373553.
44. Horoszewicz JS, Leong SS, Kawinski E, Karr JP, Rosenthal H, Chu TM, Mirand EA, Murphy GP. LNCaP model of human prostatic carcinoma. Cancer Res 1983, 43(4):1809-1818.
45. Brooks SC, Locke ER, Soule HD. Estrogen receptor in a human cell line (MCF-7) from breast carcinoma. J Biol Chem 1973, 248(17):6251-6253.
46. Goyeneche AA, Seidel EE, Telleria CM. Growth inhibition induced by antiprogestins RU-38486, ORG-31710, and CDB-2914 in ovarian cancer cells involves inhibition of cyclin dependent kinase 2. Invest New Drugs 2011,
47. Baulieu EE. The antisteroid RU486: its cellular and molecular mode of action. Trends Endocrinol Metab 1991, 2(6):233-239. 10.1016/1043-2760(91)90030-Q, 18411188.
48. Zhang S, Jonklaas J, Danielsen M. The glucocorticoid agonist activities of mifepristone (RU486) and progesterone are dependent on glucocorticoid receptor levels but not on EC50 values. Steroids 2007, 72(6-7):600-608. 10.1016/j.steroids.2007.03.012, 17509631.
49. Oakley RH, Jewell CM, Yudt MR, Bofetiado DM, Cidlowski JA. The dominant negative activity of the human glucocorticoid receptor beta isoform. Specificity and mechanisms of action. J Biol Chem 1999, 274(39):27857-27866. 10.1074/jbc.274.39.27857, 10488132.
50. Taniguchi Y, Iwasaki Y, Tsugita M, Nishiyama M, Taguchi T, Okazaki M, Nakayama S, Kambayashi M, Hashimoto K, Terada Y. Glucocorticoid receptor-beta and receptor-gamma exert dominant negative effect on gene repression but not on gene induction. Endocrinology 2010, 151(7):3204-3213. 10.1210/en.2009-1254, 20484466.
51. Yudt MR, Jewell CM, Bienstock RJ, Cidlowski JA. Molecular origins for the dominant negative function of human glucocorticoid receptor beta. Mol Cell Biol 2003, 23(12):4319-4330. 10.1128/MCB.23.12.4319-4330.2003, 156139, 12773573.
52. Lewis-Tuffin LJ, Jewell CM, Bienstock RJ, Collins JB, Cidlowski JA. Human glucocorticoid receptor beta binds RU-486 and is transcriptionally active. Mol Cell Biol 2007, 27(6):2266-2282. 10.1128/MCB.01439-06, 1820503, 17242213.
53. Kino T, Manoli I, Kelkar S, Wang Y, Su YA, Chrousos GP. Glucocorticoid receptor (GR) beta has intrinsic, GRalpha-independent transcriptional activity. Biochem Biophys Res Commun 2009, 381(4):671-675. 10.1016/j.bbrc.2009.02.110, 2796800, 19248771.
54. Rohe HJ, Ahmed IS, Twist KE, Craven RJ. PGRMC1 (progesterone receptor membrane component 1): a targetable protein with multiple functions in steroid signaling, P450 activation and drug binding. Pharmacol Ther 2009, 121(1):14-19. 10.1016/j.pharmthera.2008.09.006, 2659782, 18992768.
55. Gellersen B, Fernandes MS, Brosens JJ. Non-genomic progesterone actions in female reproduction. Hum Reprod Update 2009, 15(1):119-138.
56. Dressing GE, Goldberg JE, Charles NJ, Schwertfeger KL, Lange CA. Membrane progesterone receptor expression in mammalian tissues: A review of regulation and physiological implications. Steroids 2011, 76(1-2):11-17. 10.1016/j.steroids.2010.09.006, 20869977.
57. Thomas P, Pang Y, Dong J, Groenen P, Kelder J, de Vlieg J, Zhu Y, Tubbs C. Steroid and G protein binding characteristics of the seatrout and human progestin membrane receptor alpha subtypes and their evolutionary origins. Endocrinology 2007, 148(2):705-718.
58. Peluso JJ, Liu X, Saunders MM, Claffey KP, Phoenix K. Regulation of ovarian cancer cell viability and sensitivity to cisplatin by progesterone receptor membrane component-1. J Clin Endocrinol Metab 2008, 93(5):1592-1599. 10.1210/jc.2007-2771, 18319313.
59. Smith JL, Kupchak BR, Garitaonandia I, Hoang LK, Maina AS, Regalla LM, Lyons TJ. Heterologous expression of human mPRalpha, mPRbeta and mPRgamma in yeast confirms their ability to function as membrane progesterone receptors. Steroids 2008, 73(11):1160-1173. 10.1016/j.steroids.2008.05.003, 2597464, 18603275.
60. Parthasarathy S, Morales AJ, Murphy AA. Antioxidant: a new role for RU-486 and related compounds. J Clin Invest 1994, 94(5):1990-1995. 10.1172/JCI117551, 294624, 7962545.
61. Murphy AA, Zhou MH, Malkapuram S, Santanam N, Parthasarathy S, Sidell N. RU486-induced growth inhibition of human endometrial cells. Fertil Steril 2000, 74(5):1014-1019. 10.1016/S0015-0282(00)01606-X, 11056251.
62. Roberts CP, Parthasarathy S, Gulati R, Horowitz I, Murphy AA. Effect of RU-486 and related compounds on the proliferation of cultured macrophages. Am J Reprod Immunol 1995, 34(4):248-256.
63. Liberto M, Cobrinik D. Growth factor-dependent induction of p21(CIP1) by the green tea polyphenol, epigallocatechin gallate. Cancer Letters 2000, 154(2):151-161. 10.1016/S0304-3835(00)00378-5, 10806303.
64. Liu M, Wikonkal NM, Brash DE. Induction of cyclin-dependent kinase inhibitors and G(1) prolongation by the chemopreventive agent N-acetylcysteine. Carcinogenesis 1999, 20(9):1869-1872. 10.1093/carcin/20.9.1869, 10469636.
65. Dioufa N, Kassi E, Papavassiliou AG, Kiaris H. Atypical induction of the unfolded protein response by mifepristone. Endocrine 2010, 38(2):167-173. 10.1007/s12020-010-9362-0, 21046477.