Investigation of the effects of bicalutamide and TRAIL signaling mechanism on docetaxel resistant prostate cancer cells

Prostate cancer is the most common cancer among men, and developed metastasis spread to parts of the body. Clinically, prostate cancer can develop resistance to chemotherapy drugs, and generally, the initial treatment for metastatic prostate cancer is androgen deprivation therapy in combination with chemotherapy. This study aimed to further investigate the signaling mechanisms of Bicalutamide (BCLT) with TRAIL combination in resistance to Docetaxel (DX) on the prostate cancer cell. The human prostate cancer cell lines PC3 were generated by initially treating with DX for docetaxel resistance prostate cancer cells (PC3/DX). PC3/DX cells were transfected pAR plasmid for modeling androgen-dependent docetaxel resistance prostate cancer cells (PC3/DX/AR+) and were incubated with BCLT (2.5 μM) and/or TRAIL (2.5 ng/mL). After the treatment, cell proliferation was determined with an MTT assay. Apoptotic cells were investigated with AO/EB staining by fluorescence microscope. Levels of Caspase-3, Caspase-8, AR, TNF-α protein and gene expression were evaluated. We found apoptosis increased with TRAIL (5 ng/mL) in PC3/DX cells, whereas with the combination of 2.5 ng/mL TRAIL and BCLT (2.5 μM) in PC3/DX/AR+ cells. TNF-α protein and gene expression levels increase with TRAIL in PC3/DX and PC3/DX/AR+ cells. AR protein and gene expression levels increased with BCLT and TRAIL PC3/DX/AR+ cells. Our results indicate that BCLT and TRAIL combination has potential agents for inhibiting docetaxel resistance prostate cancer growth and metastasis.

PDF

___

[1] Poelaert F, Praet CV, Beerens AS, Meerleer GD, Fonteyne V, Ost P, Lumen N. The role of androgen receptor expression in the curative treatment of prostate cancer with radiotherapy: A pilot study. Biomed Res Int. 2015; 2015: 812815. [CrossRef]
[2] Grossmann ME, Huang H, Tindal DJ. Androgen receptor signaling in androgen-refractory prostate cancer. J Natl Cancer Inst. 2001; 93(22): 1687-1697. [CrossRef]
[3] Feldman BJ, Feldman D. The development of androgen-independent prostate cancer. Nat Rev Cancer 2001; 1(1): 34-45. [CrossRef]
[4] 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(5): 2815-2825. [CrossRef]
[5] Cai C, Wang H, Xu Y, Chen S, Balk SP. Reactivation of androgen receptor-regulated TMPRSS2:ERG gene expression in castration-resistant prostate cancer. Cancer Res. 2009; 69(15): 6027-6032. [CrossRef]
[6] Bubendorf L, Schöpfer A, Wagner U, Sauter G, Moch H, Willi N, Gasser TC, Mihatsch MJ. Metastatic patterns of prostate cancer: An autopsy study of 1,589 patients. Hum Pathol. 2000; 31(5): 578-583. [CrossRef]
[7] Vernon AE, LaBonne C. Tumor metastasis: a new twist on epithelial-mesenchymal transitions. Curr Biol. 2004; 14(17): R719-21. [CrossRef]
[8] Arya M, Bott SR, Shergill IS, Ahmed HU, Williamson M, Patel HR. The metastatic cascade in prostate cancer. Surg Oncol. 2006; 15(3): 117-128. [CrossRef]
[9] Guo C, Yeh S, Niu Y, Li g, Zheng J, Li L, Chang C. Targeting androgen receptor versus targeting androgens to suppress castration resistant prostate cancer. Cancer Lett. 2017; 397: 133-143. [CrossRef]
[10] Gjyrezi A, Xie F, Voznesensky O, Khanna P, Calagua C, Bai Y, Kung J, Wu J, Corey E, Montgomery B, Mace S, Gianolio DA, Bubley GJ, Balk SP, Giannakakou P, Bhatt RS. Taxane resistance in prostate cancer is mediated by decreased drugtarget engagement. J Clin Invest. 2020; 130(6): 3287-3298. [CrossRef]
[11] Cevik O, Acidereli H, Turut FA, Yildirim S, Acilan C. Cabazitaxel exhibits more favorable molecular changes compared to other taxanes in androgen-independent prostate cancer cells. J Biochem Mol Toxicol. 2020; e22542. [CrossRef]
[12] Smith NF, Acharya MR, Desai N, Figg (II) W, Sparreboom A. Identification of OATP1B3 as a high-affinity hepatocellular transporter of paclitaxel. Cancer Biol Ther. 2005; 4(8): 815-818. [CrossRef]
[13] Mackler NJ, Kenneth JP. Drug Insight: use of docetaxel in prostate and urothelial cancers. Nat Clin Pract Urol 2005; 2(2): 92-100. [CrossRef]
[14] Hernández-Vargas H, Palacios J, Moreno-Bueno G. Molecular profiling of docetaxel cytotoxicity in breast cancer cells: uncoupling of aberrant mitosis and apoptosis. Oncogene 2007; 26: 2902-2913. [CrossRef]
[15] Trebunova M, Laputkova G, Slaba E, Lacjakova K, Verebova A. Effects of docetaxel, doxorubicin and cyclophosphamide on human breast cancer cell line MCF-7. Anticancer Res. 2012; 32: 2849-2854. [CrossRef]
[16] Liu J, Huang Y, Zhu D, Dai Y, Liu D, Zhai Y, Liang X, Wu L, Zhao Q. Establishment and characterization of a docetaxel‑resistant human prostate cancer cell line. Oncol Lett. 2020; 20(5): Article Number:230. [CrossRef]
[17] Abe K, Kurakin A, Mohseni-maybodi M, Kay B, Khosravi-Far R. The complexity of TNF-related apoptosis-inducing ligand. Ann N Y Acad Sci. 2000; 926: 52-63. [CrossRef]
[18] Sheikh MS, Fornace AJ Jr. Death and decoy receptors and p53- mediated apoptosis. Leukemia 2000; 14(8): 1509-1513. [CrossRef]
[19] Meng RD, McDonald ER, Sheikh MS, Fornace AJ, El-Deiry WS. The TRAIL decoy receptor TRUNDD (DcR2, TRAILR4) is induced by adenovirus-p53 overexpression and can delay TRAIL-, p53-, and KILLER/DR5-dependent colon cancer apoptosis. Mol Ther. 2000; 1(2): 130-144. [CrossRef]
[20] Dalton WS, Salmon SE. Drug resistance in myeloma:mechanisms and approaches to circumvention. Hematol Oncol Clin North Am. 1992; 6: 383–393. [CrossRef]
[21] Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2002; 2: 48–58. [CrossRef]
[22] Hwang C. Overcoming docetaxel resistance in prostate cancer: a perspective review. Ther Adv Med Oncol. 2012; 4(6): 329–340. [CrossRef]
[23] Petrylak DP, Tangen CM, Hussain MH, Lara PN, Jones JA, Taplin ME, Burch PA, Berry D, Moinpour C, Kohli M, Benson MC, Small EJ, Raghavan D, Crawford ED. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004; 351(15): 1513–1520. [CrossRef]
[24] Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Theodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA, for the TAX 327 Investigators. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004; 351(15): 1502-1512. [CrossRef]
[25] Cortes JE, Pazdur R. Docetaxel. J Clin Oncol. 1995; 13(10): 2643-2655. [CrossRef]
[26] Galletti E, Magnani M, Renzulli ML, Botta M. Paclitaxel and docetaxel resistance: Molecular mechanisms and development of new generation taxanes. Chem Med Chem. 2007; 2(7): 920-942. [CrossRef]
[27] Sekino Y, Teishima J. Molecular mechanisms of docetaxel resistance in prostate cancer. Cancer Drug Resist. 2020; 3: 676-85. [CrossRef]
[28] Domingo-Domenech J, Oliva C, Rovira A, Codony-Servat J, Bosch M, Filella X, Montagut C, Tapia M, Campas C, Dang L, Rolfe M, Ross JS, Gascon P, Albanell J, Mellado B. Interleukin 6, a nuclear factor-κB target, predicts resistance to docetaxel in hormone-ındependent prostate cancer and nuclear factor-κB inhibition by PS-1145 enhances docetaxel antitumor activity. Clin Cancer Res. 2006; 12(18): 5578-5586. [CrossRef]
[29] Sprowl JA, Reed K, Armstrong SR, Lanner C, Guo B, Kalatskaya I, Stein L, Hembruff SL, Tam A, Parissenti AM. Alterations in tumor necrosis factor signaling pathways are associated with cytotoxicity and resistance to taxanes: a study in isogenic resistant tumor cells. Breast Cancer Res. 2012; 14(1): R2. [CrossRef]
[30] Ogura T, Tanaka Y, Tamaki H, Harada M. Docetaxel induces Bcl-2- and pro-apoptotic caspase-independent death of human prostate cancer DU145 cells. Int J Oncol. 2016; 48(6): 2330–2338. [CrossRef]
[31] Mediavilla-Varela M, Pacheco FJ, Almaguel F, Perez J, Sahakian E, Daniels TR , Leoh LS, Padilla A, Wall NR, Lilly MB, Leon MD, Casiano CA. Docetaxel-induced prostate cancer cell death involves concomitant activation of caspase and lysosomal pathways and is attenuated by LEDGF/p75. Mol Cancer 2009; 28: 8-68. [CrossRef]
[32] Mhaidat NM, Wang Y, Kiejda KA, Zhang XD, Hersey P. Docetaxel-induced apoptosis in melanoma cells is dependent on activation of caspase-2. Mol Cancer Ther. 2007; 6(2): 752-761. [CrossRef]
[33] Li YF, Zhang SF, Zhang TT, Li L, Gan W, Jia H-T, Xie S, Ji H-H, He D-L. Intermittent tri-weekly docetaxel plus bicalutamide in patients with castration-resistant prostate cancer: A single-arm prospective study using a historical control for comparison. Asian J Androl. 2013; 15(6): 773-779. [CrossRef]
[34] Koschny R, Walczak H, Ganten TM. The promise of TRAIL--potential and risks of a novel anticancer therapy. JMol Med. (Berl) 2007; 85: 923–935. [CrossRef]
[35] Mahalingam D, Szegezdi E, Keane M, Jong Sd; Samali A. TRAIL receptor signalling and modulation: Are we on the right TRAIL?. Cancer Treat Rev. 2009; 35(3): 280–288. [CrossRef]
[36] Munshi A, Pappas G, Honda T, McDonnell TJ, Younes A, Li Y, Meyn RE. TRAIL (APO-2L) induces apoptosis in human prostate cancer cells that is inhibitable by Bcl-2. Oncogene 2001; 20(29): 3757–3765. [CrossRef]
[37] Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ, Ashkenazi A. Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase- 8 to death receptors 4 and 5. Immunity 2000; 12(6): 611-620. [CrossRef]
[38] Kelley SK, Ashkenazi A. Targeting death receptors in cancer with Apo2L/TRAIL. Curr Opin Pharmacol. 2004; 4(4): 333-339. [CrossRef]
[39] Harith HH, Morris MJ, Kavurma MM. On the TRAIL of obesity and diabetes. Trends Endocrinol Metab. 2013; 24(11): 578-587. [CrossRef]
[40] Di Pietro R, Zauli G. Emerging non-apoptotic functions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo2L. J Cell Physiol. 2004; 201(3): 331-340. [CrossRef]
[41] LeBlanc H, Lawrence D, Varfolomeev E, Totpal K, Morlan J, Schow P, Fong S, Schwall R, Sinicropi D, Ashkenazi A. Tumor-cell resistance to death receptor-induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax. Nat Med. 2002; 8(3): 274-281. [CrossRef]
[42] Deng Y, Lin Y, Wu X. TRAIL-induced apoptosis requires Bax dependent mitochondrial release of Smac/DIABLO. Genes Dev. 2002; 16(1):33-45. [CrossRef]
[43] Ravi R, Bedi A. Requirement of BAX for TRAIL/Apo2L-induced apoptosis of colorectal cancers: synergism with sulindac-mediated inhibition of Bcl-x(L). Cancer Res. 2002; 62(6): 1583-1587. [CrossRef]
[44] Wang D, Lu J, Tindall DJ. Androgens Regulate TRAIL-induced cell death in prostate cancer cells via multiple mechanisms. Cancer Lett. 2013; 335(1): 136–144. [CrossRef]
[45] Rokhlin OW, Taghiyev AF, Guseva NV, Glover RA, Syrbu SI, Cohen MB. TRAIL-DISC formation is androgendependent in the human prostatic carcinoma cell line LNCaP. Cancer Biol Ther. 2002; 1(6): 631–637. [CrossRef]
[46] Vindrieux D, Reveiller M, Chantepie J, Yakoub S, Deschildre C ,Ruffion A, Devonec M, Benahmed M, Grataroli R. Down-regulation of DcR2 sensitizes androgen-dependent prostate cancer LNCaP cells to TRAIL-induced apoptosis. Cancer Cell Int. 2011; 11: Article Number: 42. [CrossRef]
[47] Rokhlin OW, Taghiyev AF, Guseva NV, Glover RA, Chumakov PM, Kravchenko JE, Cohen MB. Androgen regulates apoptosis induced by TNFR family ligands via multiple signaling pathways in LNCaP. Oncogene 2005; 24(45): 6773– 6784. [CrossRef]
[48] Cornforth AN, Davis JS, Khanifar E, Nastiuk K, Krolewski JJ. FOXO3a mediates the androgen-dependent regulation of FLIP and contributes to TRAIL-induced apoptosis of LNCaP cells. Oncogene 2008; 27(32): 4422–4433. [CrossRef]
[49] Walczak H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M, Chin W, Jones J, Woodward A, Le T, Smith C, Smolak P, Goodwin RG, Rauch CT, Schuh JCL, Lynch DH. Tumoricidal activity of tumor necrosis factor-related apoptosisinducing ligand in vivo. Nat Med. 1999; 5(2): 157-163. [CrossRef]
[50] Ashkenazi A, Pai RC, Fong S, Leung S, Lawrence DA, Marsters SA, Blackie C, Chang L, McMurtrey AE, Hebert A, DeForge L, Koumenis IL, Lewis D, Harris L, Bussiere J, Koeppen H, Shahrokh Z, Schwall RH. Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest. 1999; 104(2): 155-162. [CrossRef]
[51] Floyd MS Jr, Teahan SJ, Fitzpatrick JM, Watson RW. Differential mechanisms of bicalutamide-induced apoptosis in prostate cell lines. Prostate Cancer Prostatic Dis. 2011; 14(4):367. [CrossRef]
[52] Lee J, Mun S, Park A, Kim D, Heun Cha B, Kang HG. Bicalutamide enhances fodrin-mediated apoptosis through calpain in LNCaP. Exp Biol Med. (Maywood) 2018; 243(10): 843-851. [CrossRef]
[53] Li J, Xiang S, Zhang Q, Wu J, Tang Q, Zhou J, Yang L, Chen Z, Hann SS. Combination of curcumin and bicalutamide enhanced the growth inhibition of androgen-independent prostate cancer cells through SAPK/JNK and MEK/ERK1/2-mediated targeting NF-kappaB/p65 and MUC1-C. J Exp Clin Cancer Res. 2015; 34(1): 46. [CrossRef]