Antagonistic analogs of growth hormone-releasing hormone increase the efficacy of treatment of triple negative breast cancer in nude mice with doxorubicin; A preclinical study

Oncoscience

Volumn 1, Issue 10, 2014, Pages 665-673

  Perez, Roberto ^a,b   Schally, Andrew V ^a,b,c,d   Popovics, Petra ^a,b,c,e   Cai, Renzhi ^a,b,c   Sha, Wei ^a,b,c   Rincon, Ricardo ^a,b   Rick, Ferenc G ^a,b,f  

^a VETERANS AFFAIRS MEDICAL CENTER   (United States)

^b South Florida VA Foundation for Research and Education   (United States)

^c UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF MIAMI   (United States)

^e DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

^f FLORIDA INTERNATIONAL UNIVERSITY   (United States)

Author keywords

Antagonist; Combination therapy; Drug resistance; GHRH analogs; Growth hormone releasing hormone; Triple negative breast cancer

Indexed keywords

EID: 84924537778     PISSN: None     EISSN: 23314737     Source Type: Journal    
DOI: 10.18632/oncoscience.92     Document Type: Article

References (62)

1. CDC. (2010). Centers for Disease Control and Prevention: US Incidence of Breast Cancer.
2. Buchholz S, Seitz S, Schally AV, Engel JB, Rick FG, Szalontay L, Hohla F, Krishan A, Papadia A, Gaiser T, Brockhoff G, Ortmann O, Diedrich K and Koster F. Triplenegative breast cancers express receptors for luteinizing hormone-releasing hormone (LHRH) and respond to LHRH antagonist cetrorelix with growth inhibition. Int J Oncol. 2009; 35(4):789-796.
3. Dawson SJ, Provenzano E and Caldas C. Triple negative breast cancers: clinical and prognostic implications. Eur J Cancer. 2009; 45 Suppl 1(19775602):27-40.
4. Seitz S, Buchholz S, Schally AV, Jayakumar AR, Weber F, Papadia A, Rick FG, Szalontay L, Treszl A, Koster F, Ortmann O and Hohla F. Targeting triple-negative breast cancer through the somatostatin receptor with the new cytotoxic somatostatin analogue AN-162 [AEZS-124]. Anticancer Drugs. 2013; 24(2):150-157.
5. Bartsch R, Ziebermayr R, Zielinski CC and Steger GG. Triple-negative breast cancer. Wien Med Wochenschr. 2010; 160(20473728):174-181.
6. Schally AV, Varga JL and Engel JB. Antagonists of growthhormone-releasing hormone: an emerging new therapy for cancer. Nat Clin Pract Endocrinol Metab. 2008; 4(1):33-43.
7. Varga JL, Schally AV, Horvath JE, Kovacs M, Halmos G, Groot K, Toller GL, Rekasi Z and Zarandi M. Increased activity of antagonists of growth hormone-releasing hormone substituted at positions 8, 9, and 10. Proc Natl Acad Sci U S A. 2004; 101(14755056):1708-1713.
8. Szereday Z, Schally AV, Varga JL, Kanashiro CA, Hebert F, Armatis P, Groot K, Szepeshazi K, Halmos G and Busto R. Antagonists of growth hormone-releasing hormone inhibit the proliferation of experimental non-small cell lung carcinoma. Cancer Res. 2003; 63(14633721):7913-7919.
9. Weiss-Messer E, Merom O, Adi A, Karry R, Bidosee M, Ber R, Kaploun A, Stein A and Barkey RJ. Growth hormone (GH) receptors in prostate cancer: gene expression in human tissues and cell lines and characterization, GH signaling and androgen receptor regulation in LNCaP cells. Molecular and Cellular Endocrinology. 2004; 220(1-2):109-123.
10. Rick FG, Schally AV, Block NL, Nadji M, Szepeshazi K, Zarandi M, Vidaurre I, Perez R, Halmos G and Szalontay L. Antagonists of growth hormone-releasing hormone (GHRH) reduce prostate size in experimental benign prostatic hyperplasia. Proc Natl Acad Sci U S A. 2011; 108(9):3755-3760.
11. Jaszberenyi M, Rick FG, Szalontay L, Block NL, Zarandi M, Cai RZ and Schally AV. Beneficial effects of novel antagonists of GHRH in different models of Alzheimer's disease. Aging. 2012; 4(11):755-767.
12. Lucas R, Sridhar S, Rick FG, Gorshkov B, Umapathy NS, Yang G, Oseghale A, Verin AD, Chakraborty T, Matthay MA, Zemskov EA, White R, Block NL and Schally AV. Agonist of growth hormone-releasing hormone reduces pneumolysin-induced pulmonary permeability edema. Proc Natl Acad Sci U S A. 2012; 109(6):2084-2089.
13. Rick FG, Szalontay L, Schally AV, Block NL, Nadji M, Szepeshazi K, Vidaurre I, Zarandi M, Kovacs M and Rekasi Z. Combining growth hormone-releasing hormone antagonist with luteinizing hormone-releasing hormone antagonist greatly augments benign prostatic hyperplasia shrinkage. J Urol. 2012; 187(4):1498-1504.
14. Rick FG, Schally AV, Block NL, Abi-Chaker A, Krishan A and Szalontay L. Mechanisms of synergism between antagonists of growth hormone-releasing hormone and antagonists of luteinizing hormone-releasing hormone in shrinking experimental benign prostatic hyperplasia. Prostate. 2013; 73(8):873-883.
15. Rick FG, Saadat SH, Szalontay L, Block NL, Kazzazi A, Djavan B and Schally AV. Hormonal manipulation of benign prostatic hyperplasia. Curr Opin Urol. 2013; 23(1):17-24.
16. Czikora I, Sridhar S, Gorshkov B, Kasa A, Alieva I, Gonzales J, Potapenko O, Umapathy NS, Verin AD, Pillich H, Rick FG, Block NL, Chakraborty T, Matthay MA, Schally AV and Lucas R. Protective effect of Growth Hormone-Releasing Hormone agonist in bacterial toxininduced pulmonary barrier dysfunction. Frontiers in Physiology. 2014; 5.
17. Havt A, Schally AV, Halmos G, Varga JL, Toller GL, Horvath JE, Szepeshazi K, Koster F, Kovitz K, Groot K, Zarandi M and Kanashiro CA. The expression of the pituitary growth hormone-releasing hormone receptor and its splice variants in normal and neoplastic human tissues. Proc Natl Acad Sci U S A. 2005; 102(16299104):17424-17429.
18. Heinrich E, Schally AV, Buchholz S, Rick FG, Halmos G, Mile M, Groot K, Hohla F, Zarandi M and Varga JL. Dose-dependent growth inhibition in vivo of PC-3 prostate cancer with a reduction in tumoral growth factors after therapy with GHRH antagonist MZ-J-7-138. Prostate. 2008; 68(16):1763-1772.
19. Kovacs M, Schally AV, Hohla F, Rick FG, Pozsgai E, Szalontay L, Varga JL and Zarandi M. A correlation of endocrine and anticancer effects of some antagonists of GHRH. Peptides. 2010; 31(10):1839-1846.
20. Pozsgai E, Schally AV, Hocsak E, Zarandi M, Rick F and Bellyei S. The effect of a novel antagonist of growth hormone releasing hormone on cell proliferation and on the key cell signaling pathways in nine different breast cancer cell lines. Int J Oncol. 2011; 39(4):1025-1032.
21. Papadia A, Schally AV, Halmos G, Varga JL, Seitz S, Buchholz S, Rick F, Zarandi M, Bellyei S, Treszl A, Szalontay L and Lucci JA. Growth hormone-releasing hormone antagonists inhibit growth of human ovarian cancer. Horm Metab Res. 2011; 43(11):816-820.
22. Abdel-Wahab M, Schally AV, Rick FG, Szalontay L, Block NL, Jorda M, Mahmoud O, Markoe A, Shi Y-F, Reiner T, Zarandi M and Duncan R. Antagonists of growth hormone releasing hormone (GHRH) given before whole body radiation lead to modulation of radiation response and organ-specific changes in the expression of angiogenesis. J Radiat Oncol. 2012; 1(4):389-396.
23. Rick FG, Schally AV, Szalontay L, Block NL, Szepeshazi K, Nadji M, Zarandi M, Hohla F, Buchholz S and Seitz S. Antagonists of growth hormone-releasing hormone inhibit growth of androgen-independent prostate cancer through inactivation of ERK and Akt kinases. Proc Natl Acad Sci U S A. 2012; 109(5):1655-1660.
24. Rick FG, Seitz S, Schally AV, Szalontay L, Krishan A, Datz C, Stadlmayr A, Buchholz S, Block NL and Hohla F. GHRH antagonist when combined with cytotoxic agents induces S-phase arrest and additive growth inhibition of human colon cancer. Cell Cycle. 2012; 11(22):4203-4210.
25. Stangelberger A, Schally AV, Rick FG, Varga JL, Baker B, Zarandi M and Halmos G. Inhibitory effects of antagonists of growth hormone releasing hormone on experimental prostate cancers are associated with upregulation of wildtype p53 and decrease in p21 and mutant p53 proteins. Prostate. 2012; 72(5):555-565.
26. Jaszberenyi M, Schally AV, Block NL, Zarandi M, Cai RZ, Vidaurre I, Szalontay L, Jayakumar AR and Rick FG. Suppression of the proliferation of human U-87 MG glioblastoma cells by new antagonists of growth hormonereleasing hormone in vivo and in vitro. Targeted oncology. 2013; 8(4):281-290.
27. Seitz S, Rick FG, Schally AV, Treszl A, Hohla F, Szalontay L, Zarandi M, Ortmann O, Engel JB and Buchholz S. Combination of GHRH antagonists and docetaxel shows experimental effectiveness for the treatment of triplenegative breast cancers. Oncol Rep. 2013; 30(1):413-418.
28. Szalontay L, Schally AV, Popovics P, Vidaurre I, Krishan A, Zarandi M, Cai RZ, Klukovits A, Block NL and Rick FG. Novel GHRH antagonists suppress the growth of human malignant melanoma by restoring nuclear p27 function. Cell Cycle. 2014.
29. Kiaris H, Schally AV, Varga JL, Groot K and Armatis P. Growth hormone-releasing hormone: an autocrine growth factor for small cell lung carcinoma. Proc Natl Acad Sci U S A. 1999; 96(26):14894-14898.
30. Schally AV. New approaches to the therapy of various tumors based on peptide analogues. Horm Metab Res. 2008; 40(5):315-322.
31. Fahrenholtz CD, Rick FG, Garcia MI, Zarandi M, Cai RZ, Block NL, Schally AV and Burnstein KL. Preclinical efficacy of growth hormone-releasing hormone antagonists for androgen-dependent and castration-resistant human prostate cancer. Proc Natl Acad Sci U S A. 2014; 111(3):1084-1089.
32. Siriwardana G, Bradford A, Coy D and Zeitler P. Autocrine/paracrine regulation of breast cancer cell proliferation by growth hormone releasing hormone via Ras, Raf, and mitogen-activated protein kinase. Mol Endocrinol. 2006; 20(9):2010-2019.
33. Rekasi Z, Czompoly T, Schally AV and Halmos G. Isolation and sequencing of cDNAs for splice variants of growth hormone-releasing hormone receptors from human cancers. Proc Natl Acad Sci U S A. 2000; 97(19):10561-10566.
34. Csernus VJ, Schally AV, Kiaris H and Armatis P. Inhibition of growth, production of insulin-like growth factor-II (IGFII), and expression of IGF-II mRNA of human cancer cell lines by antagonistic analogs of growth hormone-releasing hormone in vitro. Proc Natl Acad Sci U S A. 1999; 96(10077643):3098-3103.
35. Kiaris H, Chatzistamou I, Schally AV, Halmos G, Varga JL, Koutselini H and Kalofoutis A. Ligand-dependent and-independent effects of splice variant 1 of growth hormonereleasing hormone receptor. Proc Natl Acad Sci U S A. 2003; 100(16):9512-9517.
36. Perez RS, AV; Vidaurre, I; Rincon, R; Block, NL; Rick, FG. Antagonists of growth hormone-releasing hormone suppress in vivo tumor growth and gene expression in triple negative breast cancers. Oncotarget. 2012; 3(9):988-997.
37. Gerger A, Renner W, Langsenlehner T, Hofmann G, Knechtel G, Szkandera J, Samonigg H, Krippl P and Langsenlehner U. Association of interleukin-10 gene variation with breast cancer prognosis. Breast Cancer Res Treat. 2010; 119(19437115):701-705.
38. Tawara K, Oxford JT and Jorcyk CL. Clinical significance of interleukin (IL)-6 in cancer metastasis to bone: potential of anti-IL-6 therapies. Cancer Manag Res. 2011; 3(21625400):177-189.
39. Zhao X, Sun X, Gao F, Luo J and Sun Z. Effects of ulinastatin and docataxel on breast tumor growth and expression of IL-6, IL-8, and TNF-alpha. J Exp Clin Cancer Res. 2011; 30(1):22.
40. Szepeshazi K, Schally AV, Block NL, Halmos G, Nadji M, Szalontay L, Vidaurre I, Abi-Chaker A and Rick FG. Powerful inhibition of experimental human pancreatic cancers by receptor targeted cytotoxic LH-RH analog AEZS-108. Oncotarget. 2013; 4(5):751-760.
41. Schally AV, Varga JL and Engel JB. Antagonists of growthhormone-releasing hormone: an emerging new therapy for cancer. Nature Clinical Practice Endocrinology & Metabolism. 2008; 4(1):33-43.
42. Khorram O, Garthwaite M, Grosen E and Golos T. Human uterine and ovarian expression of growth hormonereleasing hormone messenger RNA in benign and malignant gynecologic conditions. Fertil Steril. 2001; 75(11163834):174-179.
43. Hohla F, Schally AV, Szepeshazi K, Varga JL, Buchholz S, Koster F, Heinrich E, Halmos G, Rick FG, Kannadka C, Datz C and Kanashiro CA. Synergistic inhibition of growth of lung carcinomas by antagonists of growth hormonereleasing hormone in combination with docetaxel. Proc Natl Acad Sci U S A. 2006; 103(16983095):14513-14518.
44. Kanashiro CA, Schally AV, Groot K, Armatis P, Bernardino ALF and Varga JL. Inhibition of mutant p53 expression and growth of DMS-153 small cell lung carcinoma by antagonists of growth hormone-releasing hormone and bombesin. Proc Natl Acad Sci U S A. 2003; 100(14660794):15836-15841.
45. Maitland NJ and Collins AT. Prostate Cancer Stem Cells: A New Target for Therapy. Journal of Clinical Oncology. 2008; 26(17):2862-2870.
46. Pradhan M, Bembinster LA, Baumgarten SC and Frasor J. Proinflammatory cytokines enhance estrogen-dependent expression of the multidrug transporter gene ABCG2 through estrogen receptor and NF{kappa}B cooperativity at adjacent response elements. J Biol Chem. 2010; 285(41):31100-31106.
47. Sullivan NJ, Sasser AK, Axel AE, Vesuna F, Raman V, Ramirez N, Oberyszyn TM and Hall BM. Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human breast cancer cells. Oncogene. 2009; 28(19581928):2940-2947.
48. Iliopoulos D, Hirsch HA, Wang G and Struhl K. Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion. Proc Natl Acad Sci U S A. 2011; 108(21220315):1397-1402.
49. Guo W, Lasky JL, Chang C-J, Mosessian S, Lewis X, Xiao Y, Yeh JE, Chen JY, Iruela-Arispe ML, Varella-Garcia M and Wu H. Multi-genetic events collaboratively contribute to Pten-null leukaemia stem-cell formation. Nature. 2008; 453(18463637):529-533.
50. Lopez-Novoa JM and Nieto MA. Inflammation and EMT: an alliance towards organ fibrosis and cancer progression. EMBO Mol Med. 2009; 1(6-7):303-314.
51. Hugo H, Ackland ML, Blick T, Lawrence MG, Clements JA, Williams ED and Thompson EW. Epithelial-mesenchymal and mesenchymal-epithelial transitions in carcinoma progression. J Cell Physiol. 2007; 213(2):374-383.
52. Soria G, Ofri-Shahak M, Haas I, Yaal-Hahoshen N, Leider-Trejo L, Leibovich-Rivkin T, Weitzenfeld P, Meshel T, Shabtai E, Gutman M and Ben-Baruch A. Inflammatory mediators in breast cancer: Coordinated expression of TNFa & IL-1ß with CCL2 & CCL5 and effects on epithelial-tomesenchymal transition. BMC Cancer. 2011; 11(1):130.
53. Rick FG, Schally AV, Block NL, Nadji M, Szepeshazi K, Zarandi M, Vidaurre I, Perez R, Halmos G and Szalontay L. Antagonists of growth hormone-releasing hormone (GHRH) reduce prostate size in experimental benign prostatic hyperplasia. Proc Natl Acad Sci U S A. 2011; 108(21321192):3755-3760.
54. Hohla F, Winder T, Greil R, Rick FG, Block NL and Schally AV. Targeted therapy in advanced metastatic colorectal cancer: Current concepts and perspectives. World journal of gastroenterology: WJG. 2014; 20(20):6102-6112.
55. Hohla F, Buchholz S, Schally AV, Seitz S, Rick FG, Szalontay L, Varga JL, Zarandi M, Halmos G, Vidaurre I, Krishan A, Kurtoglu M, Chandna S, Aigner E and Datz C. GHRH antagonist causes DNA damage leading to p21 mediated cell cycle arrest and apoptosis in human colon cancer cells. Cell Cycle. 2009; 8(19):3149-3156.
56. Rick FG, Abi-Chaker A, Szalontay L, Perez R, Jaszberenyi M, Jayakumar AR, Shamaladevi N, Szepeshazi K, Vidaurre I, Halmos G, Krishan A, Block NL and Schally AV. Shrinkage of experimental benign prostatic hyperplasia and reduction of prostatic cell volume by a gastrin-releasing peptide antagonist. Proc Natl Acad Sci U S A. 2013; 110(7):2617-2622.
57. Seitz S, Hohla F, Schally AV, Moder A, Engel JB, Horn F, Varga J, Zarandi M, Ortmann O, Koster F and Buchholz S. Inhibition of estrogen receptor positive and negative breast cancer cell lines with a growth hormone-releasing hormone antagonist. Oncol Rep. 2008; 20(5):1289-1294.
58. Koster F, Engel JB, Schally AV, Honig A, Schroer A, Seitz S, Hohla F, Ortmann O, Diedrich K and Buchholz S. Triple-negative breast cancers express receptors for growth hormone-releasing hormone (GHRH) and respond to GHRH antagonists with growth inhibition. Breast Cancer Res Treat. 2009; 116(2):273-279.
59. Zarandi M, Horvath JE, Halmos G, Pinski J, Nagy A, Groot K, Rekasi Z and Schally AV. Synthesis and biological activities of highly potent antagonists of growth hormonereleasing hormone. Proc Natl Acad Sci U S A. 1994; 91(25):12298-12302.
60. Rick FG, Buchholz S, Schally AV, Szalontay L, Krishan A, Datz C, Stadlmayr A, Aigner E, Perez R, Seitz S, Block NL and Hohla F. Combination of gastrin-releasing peptide antagonist with cytotoxic agents produces synergistic inhibition of growth of human experimental colon cancers. Cell Cycle. 2012; 11(13):2518-2525.
61. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A and Speleman F. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002; 3(7):RESEARCH0034.
62. Szepeshazi K, Schally AV, Keller G, Block NL, Benten D, Halmos G, Szalontay L, Vidaurre I, Jaszberenyi M and Rick FG. Receptor-targeted therapy of human experimental urinary bladder cancers with cytotoxic LH-RH analog AN-152 [AEZS-108]. Oncotarget. 2012; 3(7):686-699.