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Overcoming resistance to TRAIL-induced apoptosis in solid tumor cells by simultaneously targeting death receptors, c-FLIP and IAPs

  • Authors:
    • Ying Huang
    • Xiang Yang
    • Tianrui Xu
    • Qinghong Kong
    • Yaping Zhang
    • Yuehai Shen
    • Yunlin Wei
    • Guanlin Wang
    • Kwen-Jen Chang
  • View Affiliations / Copyright

    Affiliations: Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China
    Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 153-163
    |
    Published online on: May 16, 2016
       https://doi.org/10.3892/ijo.2016.3525
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Abstract

The discovery of the TRAIL protein and its death receptors DR4/5 changed the horizon of cancer research because TRAIL specifically kills cancer cells. However, the validity of TRAIL-based cancer therapies has yet to be established, as most cancer cells are TRAIL-resistant. In this report, we demonstrate that TRAIL-resistance of many cancer cell lines can be overcome after siRNA- or rocaglamide-mediated downregulation of c-FLIP expression and simultaneous inhibition of IAPs activity using AT406, a pan-antagonist of IAPs. Combined triple actions of the TRAIL, the IAPs inhibitor, AT406, and the c-FLIP expression inhibitor, rocaglamide (ART), markedly improve TRAIL-induced apoptotic effects in most solid cancer cell lines through the activation of an extrinsic apoptosis pathway. Furthermore, this ART combination does not harm normal cells. Among the 18 TRAIL-resistant cancer cell lines used, 15 cell lines become sensitive or highly sensitive to ART, and two out of three glioma cell lines exhibit high resistance to ART treatment due to very low levels of procaspase-8. This study provides a rationale for the development of TRAIL-induced apoptosis-based cancer therapies.
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View References

1 

Tannock IF: Cancer: Resistance through repopulation. Nature. 517:152–153. 2015. View Article : Google Scholar

2 

Santarpia L, Lippman SM and El-Naggar AK: Targeting the MAPK-RAS-RAF signaling pathway in cancer therapy. Expert Opin Ther Targets. 16:103–119. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Sriraman SK, Aryasomayajula B and Torchilin VP: Barriers to drug delivery in solid tumors. Tissue Barriers. 2:e295282014. View Article : Google Scholar : PubMed/NCBI

4 

Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA, et al: Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity. 3:673–682. 1995. View Article : Google Scholar : PubMed/NCBI

5 

Pitti RM, Marsters SA, Ruppert S, Donahue CJ, Moore A and Ashkenazi A: Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J Biol Chem. 271:12687–12690. 1996. View Article : Google Scholar : PubMed/NCBI

6 

Ashkenazi A, Pai RC, Fong S, Leung S, Lawrence DA, Marsters SA, Blackie C, Chang L, McMurtrey AE, Hebert A, et al: Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest. 104:155–162. 1999. View Article : Google Scholar : PubMed/NCBI

7 

Takeda K, Hayakawa Y, Smyth MJ, Kayagaki N, Yamaguchi N, Kakuta S, Iwakura Y, Yagita H and Okumura K: Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells. Nat Med. 7:94–100. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ and Ashkenazi A: Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity. 12:611–620. 2000. View Article : Google Scholar : PubMed/NCBI

9 

Lemke J, von Karstedt S, Zinngrebe J and Walczak H: Getting TRAIL back on track for cancer therapy. Cell Death Differ. 21:1350–1364. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Holland PM: Death receptor agonist therapies for cancer, which is the right TRAIL? Cytokine Growth Factor Rev. 25:185–193. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Dyer MJ, MacFarlane M and Cohen GM: Barriers to effective TRAIL-targeted therapy of malignancy. J Clin Oncol. 25:4505–4506. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Koschny R, Walczak H and Ganten TM: The promise of TRAIL - potential and risks of a novel anticancer therapy. J Mol Med Berl. 85:923–935. 2007. View Article : Google Scholar

13 

Salvesen GS and Duckett CS: IAP proteins: Blocking the road to death's door. Nat Rev Mol Cell Biol. 3:401–410. 2002. View Article : Google Scholar : PubMed/NCBI

14 

Fulda S: Inhibitor of apoptosis proteins as targets for anticancer therapy. Expert Rev Anticancer Ther. 7:1255–1264. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Cai Q, Sun H, Peng Y, Lu J, Nikolovska-Coleska Z, McEachern D, Liu L, Qiu S, Yang CY, Miller R, et al: A potent and orally active antagonist (SM-406/AT-406) of multiple inhibitor of apoptosis proteins (IAPs) in clinical development for cancer treatment. J Med Chem. 54:2714–2726. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Fulda S, Wick W, Weller M and Debatin KM: Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo. Nat Med. 8:808–815. 2002.PubMed/NCBI

17 

Fakler M, Loeder S, Vogler M, Schneider K, Jeremias I, Debatin KM and Fulda S: Small molecule XIAP inhibitors cooperate with TRAIL to induce apoptosis in childhood acute leukemia cells and overcome Bcl-2-mediated resistance. Blood. 113:1710–1722. 2009. View Article : Google Scholar

18 

Vogler M, Walczak H, Stadel D, Haas TL, Genze F, Jovanovic M, Bhanot U, Hasel C, Möller P, Gschwend JE, et al: Small molecule XIAP inhibitors enhance TRAIL-induced apoptosis and antitumor activity in preclinical models of pancreatic carcinoma. Cancer Res. 69:2425–2434. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, Bodmer JL, Schröter M, Burns K, Mattmann C, et al: Inhibition of death receptor signals by cellular FLIP. Nature. 388:190–195. 1997. View Article : Google Scholar : PubMed/NCBI

20 

Aoudjit F and Vuori K: Integrin signaling in cancer cell survival and chemoresistance. Chemother Res Pract. 2012:2831812012.PubMed/NCBI

21 

Safa AR and Pollok KE: Targeting the anti-apoptotic protein c-FLIP for cancer therapy. Cancers (Basel). 3. pp. 1639–1671. 2011, View Article : Google Scholar

22 

Chawla-Sarkar M, Bae SI, Reu FJ, Jacobs BS, Lindner DJ and Borden EC: Downregulation of Bcl-2, FLIP or IAPs (XIAP and survivin) by siRNAs sensitizes resistant melanoma cells to Apo2L/TRAIL-induced apoptosis. Cell Death Differ. 11:915–923. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Bleumink M, Köhler R, Giaisi M, Proksch P, Krammer PH and Li-Weber M: Rocaglamide breaks TRAIL resistance in HTLV-1-associated adult T-cell leukemia/lymphoma by translational suppression of c-FLIP expression. Cell Death Differ. 18:362–370. 2011. View Article : Google Scholar :

24 

Zhu JY, Giaisi M, Köhler R, Müller WW, Mühleisen A, Proksch P, Krammer PH and Li-Weber M: Rocaglamide sensitizes leukemic T cells to activation-induced cell death by differential regulation of CD95L and c-FLIP expression. Cell Death Differ. 16:1289–1299. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Giaisi M, Kohler R, Fulda S, Krammer PH and Li-Weber M: Rocaglamide and a XIAP inhibitor cooperatively sensitize TRAIL-mediated apoptosis in Hodgkin's lymphomas. Int J Cancer. 131:1003–1008. 2012. View Article : Google Scholar

26 

Gronthos S, Mankani M, Brahim J, Robey PG and Shi S: Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA. 97:13625–13630. 2000. View Article : Google Scholar : PubMed/NCBI

27 

Zhang YP, Kong QH, Huang Y, Wang GL and Chang KJ: Inhibition of c-FLIP by RNAi enhances sensitivity of the human osteogenic sarcoma cell line U2OS to TRAIL-induced apoptosis. Asian Pac J Cancer Prev. 16:2251–2256. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Ziauddin MF, Yeow WS, Maxhimer JB, Baras A, Chua A, Reddy RM, Tsai W, Cole GW Jr, Schrump DS and Nguyen DM: Valproic acid, an antiepileptic drug with histone deacetylase inhibitory activity, potentiates the cytotoxic effect of Apo2L/TRAIL on cultured thoracic cancer cells through mitochondria-dependent caspase activation. Neoplasia. 8:446–457. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Micheau O, Shirley S and Dufour F: Death receptors as targets in cancer. Br J Pharmacol. 169:1723–1744. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Wiezorek J, Holland P and Graves J: Death receptor agonists as a targeted therapy for cancer. Clin Cancer Res. 16:1701–1708. 2010. View Article : Google Scholar : PubMed/NCBI

31 

Graves JD, Kordich JJ, Huang TH, Piasecki J, Bush TL, Sullivan T, Foltz IN, Chang W, Douangpanya H, Dang T, et al: Apo2L/TRAIL and the death receptor 5 agonist antibody AMG 655 cooperate to promote receptor clustering and antitumor activity. Cancer Cell. 26:177–189. 2014. View Article : Google Scholar : PubMed/NCBI

32 

Fulda S: Safety and tolerability of TRAIL receptor agonists in cancer treatment. Eur J Clin Pharmacol. 71:525–527. 2015. View Article : Google Scholar : PubMed/NCBI

33 

Sayers TJ: Targeting the extrinsic apoptosis signaling pathway for cancer therapy. Cancer Immunol Immunother. 60:1173–1180. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Menke C, Bin L, Thorburn J, Behbakht K, Ford HL and Thorburn A: Distinct TRAIL resistance mechanisms can be overcome by proteasome inhibition but not generally by synergizing agents. Cancer Res. 71:1883–1892. 2011. View Article : Google Scholar : PubMed/NCBI

35 

Daniel PT, Wieder T, Sturm I and Schulze-Osthoff K: The kiss of death: Promises and failures of death receptors and ligands in cancer therapy. Leukemia. 15:1022–1032. 2001. View Article : Google Scholar : PubMed/NCBI

36 

Schneider P, Olson D, Tardivel A, Browning B, Lugovskoy A, Gong D, Dobles M, Hertig S, Hofmann K, Van Vlijmen H, et al: Identification of a new murine tumor necrosis factor receptor locus that contains two novel murine receptors for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). J Biol Chem. 278:5444–5454. 2003. View Article : Google Scholar

37 

Wu GS, Burns TF, Zhan Y, Alnemri ES and El-Deiry WS: Molecular cloning and functional analysis of the mouse homologue of the KILLER/DR5 tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor. Cancer Res. 59:2770–2775. 1999.PubMed/NCBI

38 

van Dijk M, Halpin-McCormick A, Sessler T, Samali A and Szegezdi E: Resistance to TRAIL in non-transformed cells is due to multiple redundant pathways. Cell Death Dis. 4:e7022013. View Article : Google Scholar : PubMed/NCBI

39 

Jänicke RU, Sprengart ML, Wati MR and Porter AG: Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem. 273:9357–9360. 1998. View Article : Google Scholar : PubMed/NCBI

40 

Yang XH, Sladek TL, Liu X, Butler BR, Froelich CJ and Thor AD: Reconstitution of caspase 3 sensitizes MCF-7 breast cancer cells to doxorubicin- and etoposide-induced apoptosis. Cancer Res. 61:348–354. 2001.PubMed/NCBI

41 

Eggert A, Grotzer MA, Zuzak TJ, Wiewrodt BR, Ho R, Ikegaki N and Brodeur GM: Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in neuroblastoma cells correlates with a loss of caspase-8 expression. Cancer Res. 61:1314–1319. 2001.PubMed/NCBI

42 

Hopkins-Donaldson S, Ziegler A, Kurtz S, Bigosch C, Kandioler D, Ludwig C, Zangemeister-Wittke U and Stahel R: Silencing of death receptor and caspase-8 expression in small cell lung carcinoma cell lines and tumors by DNA methylation. Cell Death Differ. 10:356–364. 2003. View Article : Google Scholar : PubMed/NCBI

43 

Duiker EW, Meijer A, van der Bilt ARM, Meersma GJ, Kooi N, van der Zee AG, de Vries EG and de Jong S: Drug-induced caspase 8 upregulation sensitises cisplatin-resistant ovarian carcinoma cells to rhTRAIL-induced apoptosis. Br J Cancer. 104:1278–1287. 2011. View Article : Google Scholar : PubMed/NCBI

44 

Jia SH, Parodo J, Kapus A, Rotstein OD and Marshall JC: Dynamic regulation of neutrophil survival through tyrosine phosphorylation or dephosphorylation of caspase-8. J Biol Chem. 283:5402–5413. 2008. View Article : Google Scholar

45 

Jin Z, Li Y, Pitti R, Lawrence D, Pham VC, Lill JR and Ashkenazi A: Cullin3-based polyubiquitination and p62-dependent aggregation of caspase-8 mediate extrinsic apoptosis signaling. Cell. 137:721–735. 2009. View Article : Google Scholar : PubMed/NCBI

46 

Bellail AC, Olson JJ, Yang X, Chen ZJ and Hao C: A20 ubiquitin ligase-mediated polyubiquitination of RIP1 inhibits caspase-8 cleavage and TRAIL-induced apoptosis in glioblastoma. Cancer Discov. 2:140–155. 2012. View Article : Google Scholar : PubMed/NCBI

47 

Fulda S, Küfer MU, Meyer E, van Valen F, Dockhorn-Dworniczak B and Debatin KM: Sensitization for death receptor- or drug-induced apoptosis by re-expression of caspase-8 through demethylation or gene transfer. Oncogene. 20:5865–5877. 2001. View Article : Google Scholar : PubMed/NCBI

48 

Casciano I, De Ambrosis A, Croce M, Pagnan G, Di Vinci A, Allemanni G, Banelli B, Ponzoni M, Romani M and Ferrini S: Expression of the caspase-8 gene in neuroblastoma cells is regulated through an essential interferon-sensitive response element (ISRE). Cell Death Differ. 11:131–134. 2004. View Article : Google Scholar

49 

Fulda S and Debatin KM: IFNgamma sensitizes for apoptosis by upregulating caspase-8 expression through the Stat1 pathway. Oncogene. 21:2295–2308. 2002. View Article : Google Scholar : PubMed/NCBI

50 

Crowder RN and El-Deiry WS: Caspase-8 regulation of TRAIL-mediated cell death. Exp Oncol. 34:160–164. 2012.PubMed/NCBI

51 

Soung YH, Lee JW, Kim SY, Sung YJ, Park WS, Nam SW, Kim SH, Lee JY, Yoo NJ and Lee SH: Caspase-8 gene is frequently inactivated by the frameshift somatic mutation 1225_1226delTG in hepatocellular carcinomas. Oncogene. 24:141–147. 2005. View Article : Google Scholar

52 

Shirley S and Micheau O: Targeting c-FLIP in cancer. Cancer Lett. 332:141–150. 2013. View Article : Google Scholar

53 

Wajant H, Haas E, Schwenzer R, Muhlenbeck F, Kreuz S, Schubert G, Grell M, Smith C and Scheurich P: Inhibition of death receptor-mediated gene induction by a cycloheximide-sensitive factor occurs at the level of or upstream of Fas-associated death domain protein (FADD). J Biol Chem. 275:24357–24366. 2000. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Huang Y, Yang X, Xu T, Kong Q, Zhang Y, Shen Y, Wei Y, Wang G and Chang K: Overcoming resistance to TRAIL-induced apoptosis in solid tumor cells by simultaneously targeting death receptors, c-FLIP and IAPs. Int J Oncol 49: 153-163, 2016.
APA
Huang, Y., Yang, X., Xu, T., Kong, Q., Zhang, Y., Shen, Y. ... Chang, K. (2016). Overcoming resistance to TRAIL-induced apoptosis in solid tumor cells by simultaneously targeting death receptors, c-FLIP and IAPs. International Journal of Oncology, 49, 153-163. https://doi.org/10.3892/ijo.2016.3525
MLA
Huang, Y., Yang, X., Xu, T., Kong, Q., Zhang, Y., Shen, Y., Wei, Y., Wang, G., Chang, K."Overcoming resistance to TRAIL-induced apoptosis in solid tumor cells by simultaneously targeting death receptors, c-FLIP and IAPs". International Journal of Oncology 49.1 (2016): 153-163.
Chicago
Huang, Y., Yang, X., Xu, T., Kong, Q., Zhang, Y., Shen, Y., Wei, Y., Wang, G., Chang, K."Overcoming resistance to TRAIL-induced apoptosis in solid tumor cells by simultaneously targeting death receptors, c-FLIP and IAPs". International Journal of Oncology 49, no. 1 (2016): 153-163. https://doi.org/10.3892/ijo.2016.3525
Copy and paste a formatted citation
x
Spandidos Publications style
Huang Y, Yang X, Xu T, Kong Q, Zhang Y, Shen Y, Wei Y, Wang G and Chang K: Overcoming resistance to TRAIL-induced apoptosis in solid tumor cells by simultaneously targeting death receptors, c-FLIP and IAPs. Int J Oncol 49: 153-163, 2016.
APA
Huang, Y., Yang, X., Xu, T., Kong, Q., Zhang, Y., Shen, Y. ... Chang, K. (2016). Overcoming resistance to TRAIL-induced apoptosis in solid tumor cells by simultaneously targeting death receptors, c-FLIP and IAPs. International Journal of Oncology, 49, 153-163. https://doi.org/10.3892/ijo.2016.3525
MLA
Huang, Y., Yang, X., Xu, T., Kong, Q., Zhang, Y., Shen, Y., Wei, Y., Wang, G., Chang, K."Overcoming resistance to TRAIL-induced apoptosis in solid tumor cells by simultaneously targeting death receptors, c-FLIP and IAPs". International Journal of Oncology 49.1 (2016): 153-163.
Chicago
Huang, Y., Yang, X., Xu, T., Kong, Q., Zhang, Y., Shen, Y., Wei, Y., Wang, G., Chang, K."Overcoming resistance to TRAIL-induced apoptosis in solid tumor cells by simultaneously targeting death receptors, c-FLIP and IAPs". International Journal of Oncology 49, no. 1 (2016): 153-163. https://doi.org/10.3892/ijo.2016.3525
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