Ritonavir, nelfinavir, saquinavir and lopinavir induce proteotoxic stress in acute myeloid leukemia cells and sensitize them for proteasome inhibitor treatment at low micromolar drug concentrations

Leukemia Research

Volumn 38, Issue 3, 2014, Pages 383-392

  Kraus, Marianne ^a   Müller Ide, Hendrik ^b   Rückrich, Thomas ^b   Bader, Jürgen ^a   Overkleeft, Herman ^c   Driessen, Christoph ^a,b  

^a CANTONAL HOSPITAL ST GALLEN   (Switzerland)

^b UNIVERSITY OF TÜBINGEN   (Germany)

^c LEIDEN UNIVERSITY   (Netherlands)

Author keywords

Acute myeloid leukemia; HIV protease inhibitor; Proteasome inhibitions; Unfolded protein response

Indexed keywords

ACUTE MYELOID LEUKEMIA; HIV PROTEASE INHIBITOR; PROTEASOME INHIBITIONS; UNFOLDED PROTEIN RESPONSE;

APOPTOSIS; CYTOTOXINS; DRUG RESISTANCE, NEOPLASM; DRUG SYNERGISM; GENE EXPRESSION REGULATION, LEUKEMIC; HIV PROTEASE INHIBITORS; HUMANS; LEUKEMIA, MYELOID, ACUTE; LOPINAVIR; NELFINAVIR; PHOSPHORYLATION; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEASOME INHIBITORS; PROTO-ONCOGENE PROTEINS C-AKT; RITONAVIR; SAQUINAVIR; SIGNAL TRANSDUCTION; TUMOR CELLS, CULTURED;

EID: 84894233069     PISSN: 01452126     EISSN: 18735835     Source Type: Journal    
DOI: 10.1016/j.leukres.2013.12.017     Document Type: Article

References (42)

1. Kantarjian H.M., Thomas X.G., Dmoszynska A., Wierzbowska A., Mazur G., Mayer J., et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol 2012, 30(21):2670-2677.
2. Gausdal G., Gjertsen B.T., McCormack E., Van D.P., Hovland R., Krakstad C., et al. Abolition of stress-induced protein synthesis sensitizes leukemia cells to anthracycline-induced death. Blood 2008, 111(5):2866-2877.
3. Hagner P.R., Schneider A., Gartenhaus R.B. Targeting the translational machinery as a novel treatment strategy for hematologic malignancies. Blood 2010, 115(11):2127-2135.
4. Zhang K., Kaufman R.J. Identification and characterization of endoplasmic reticulum stress-induced apoptosis in vivo. Methods Enzymol 2008, 442:395-419.
5. Goldberg A.L. Protein degradation protection against misfolded or damaged proteins. Nature 2003, 426(6968):895-899.
6. Grant S. Enhancing proteotoxic stress as an anticancer strategy. Oncotarget 2011, 2(4):284-286.
7. Workman P., Davies F.E. A stressful life (or death): combinatorial proteotoxic approaches to cancer-selective therapeutic vulnerability. Oncotarget 2011, 2(4):277-280.
8. Haefliger S., Klebig C., Schaubitzer K., Schardt J., Timchenko N., Mueller B.U., et al. Protein disulfide isomerase blocks CEBPA translation and is up-regulated during the unfolded protein response in AML. Blood 2011, 117(22):5931-5940.
9. Schardt J.A., Weber D., Eyholzer M., Mueller B.U., Pabst T. Activation of the unfolded protein response is associated with favorable prognosis in acute myeloid leukemia. Clin Cancer Res 2009, 15(11):3834-3841.
10. Neznanov N., Komarov A.P., Neznanova L., Stanhope-Baker P., Gudkov A.V. Proteotoxic stress targeted therapy (PSTT): induction of protein misfolding enhances the antitumor effect of the proteasome inhibitor bortezomib. Oncotarget 2011, 2(3):209-221.
11. Dewan M.Z., Uchihara J.N., Terashima K., Honda M., Sata T., Ito M., et al. Efficient intervention of growth and infiltration of primary adult T-cell leukemia cells by an HIV protease inhibitor, ritonavir. Blood 2006, 107(2):716-724.
12. Dewan M.Z., Tomita M., Katano H., Yamamoto N., Ahmed S., Yamamoto M., et al. An HIV protease inhibitor, ritonavir targets the nuclear factor-kappaB and inhibits the tumor growth and infiltration of EBV-positive lymphoblastoid B cells. Int J Cancer 2009, 124(3):622-629.
13. Ikezoe T., Daar E.S., Hisatake J., Taguchi H., Koeffler H.P. HIV-1 protease inhibitors decrease proliferation and induce differentiation of human myelocytic leukemia cells. Blood 2000, 96(10):3553-3559.
14. Ikezoe T., Saito T., Bandobashi K., Yang Y., Koeffler H.P., Taguchi H. HIV-1 protease inhibitor induces growth arrest and apoptosis of human multiple myeloma cells via inactivation of signal transducer and activator of transcription 3 and extracellular signal-regulated kinase 1/2. Mol Cancer Ther 2004, 3(4):473-479.
15. Timeus F., Crescenzio N., Ricotti E., Doria A., Bertin D., Saglio G., et al. The effects of saquinavir on imatinib-resistant chronic myelogenous leukemia cell lines. Haematologica 2006, 91(5):711-712.
16. Bono C., Karlin L., Harel S., Mouly E., Labaume S., Galicier L., et al. The HIV-1 protease inhibitor nelfinavir impairs proteasome activity and inhibits the multiple myeloma cells proliferation in vitro and in vivo. Haematologica 2012, 97(7):1101-1109.
17. Chow W.A., Jiang C., Guan M. Anti-HIV drugs for cancer therapeutics: back to the future?. Lancet Oncol 2009, 10(1):61-71.
18. Stebbing J., Bower M. The anti-tumor effects of human immunodeficiency virus protease inhibitors: ready for real time?. Int J Cancer 2011, 128(1):1-2.
19. Laurent N., de B.S., Guillamo J.S., Christov C., Zini R., Jouault H., et al. Effects of the proteasome inhibitor ritonavir on glioma growth in vitro and in vivo. Mol Cancer Ther 2004, 3(2):129-136.
20. Guan M., Fousek K., Jiang C., Guo S., Synold T., Xi B., et al. Nelfinavir induces liposarcoma apoptosis through inhibition of regulated intramembrane proteolysis of SREBP-1 and ATF6. Clin Cancer Res 2011, 17(7):1796-1806.
21. Guan M., Fousek K., Chow W.A. Nelfinavir inhibits regulated intramembrane proteolysis of sterol regulatory element binding protein-1 and activating transcription factor 6 in castration-resistant prostate cancer. FEBS J 2012, 279(13):2399-2400.
22. Shim J.S., Rao R., Beebe K., Neckers L., Han I., Nahta R., et al. Selective inhibition of HER2-positive breast cancer cells by the HIV protease inhibitor nelfinavir. J Natl Cancer Inst 2012, 104(20):1576-1590.
23. Guzman M.L., Swiderski C.F., Howard D.S., Grimes B.A., Rossi R.M., Szilvassy S.J., et al. Preferential induction of apoptosis for primary human leukemic stem cells. Proc Natl Acad Sci USA 2002, 99(25):16220-51622.
24. Kawabata S., Gills J.J., Mercado-Matos J.R., Lopiccolo J., Wilson W., Hollander M.C., et al. Synergistic effects of nelfinavir and bortezomib on proteotoxic death of NSCLC and multiple myeloma cells. Cell Death Dis 2012, 3:e353.
25. Kraus M., Ruckrich T., Reich M., Gogel J., Beck A., Kammer W., et al. Activity patterns of proteasome subunits reflect bortezomib sensitivity of hematologic malignancies and are variable in primary human leukemia cells. Leukemia 2007, 21(1):84-92.
26. Kraus M., Malenke E., Gogel J., Muller H., Ruckrich T., Overkleeft H., et al. Ritonavir induces endoplasmic reticulum stress and sensitizes sarcoma cells toward bortezomib-induced apoptosis. Mol Cancer Ther 2008, 7(7):1940-1948.
27. Glas R., Bogyo M., McMaster J.S., Gaczynska M., Ploegh H.L. A proteolytic system that compensates for loss of proteasome function. Nature 1998, 392(6676):618-622.
28. Tebas P., Powderly W.G. Nelfinavir mesylate. Expert Opin Pharmacother 2000, 1(7):1429-1440.
29. Berkers C.R., Verdoes M., Lichtman E., Fiebiger E., Kessler B.M., Anderson K.C., et al. Activity probe for in vivo profiling of the specificity of proteasome inhibitor bortezomib. Nat Methods 2005, 2(5):357-362.
30. Greiner A., Lautwein A., Overkleeft H.S., Weber E., Driessen C. Activity and subcellular distribution of cathepsins in primary human monocytes. J Leukoc Biol 2003, 73(2):235-242.
31. Chou T.C. Theoretical basis experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev 2006, 58(3):621-681.
32. Ruckrich T., Kraus M., Gogel J., Beck A., Ovaa H., Verdoes M., et al. Characterization of the ubiquitin-proteasome system in bortezomib-adapted cells. Leukemia 2009, 23(6):1098-1105.
33. Park G.B., Kim Y.S., Lee H.K., Song H., Cho D.H., Lee W.J., et al. Endoplasmic reticulum stress-mediated apoptosis of EBV-transformed B cells by cross-linking of CD70 is dependent upon generation of reactive oxygen species and activation of p38 MAPK and JNK pathway. J Immunol 2010, 185(12):7274-7284.
34. Hitomi J., Katayama T., Eguchi Y., Kudo T., Taniguchi M., Koyama Y., et al. Involvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and Abeta-induced cell death. J Cell Biol 2004, 165(3):347-356.
35. Gills J.J., Lopiccolo J., Tsurutani J., Shoemaker R.H., Best C.J., Abu-Asab M.S., et al. Nelfinavir, a lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that induces endoplasmic reticulum stress, autophagy, and apoptosis in vitro and in vivo. Clin Cancer Res 2007, 13(17):5183-5194.
36. Gaedicke S., Firat-Geier E., Constantiniu O., Lucchiari-Hartz M., Freudenberg M., Galanos C., et al. Antitumor effect of the human immunodeficiency virus protease inhibitor ritonavir: induction of tumor-cell apoptosis associated with perturbation of proteasomal proteolysis. Cancer Res 2002, 62(23):6901-6908.
37. Ikezoe T., Bandobashi K., Yang Y., Takeuchi S., Sekiguchi N., Sakai S., et al. HIV-1 protease inhibitor ritonavir potentiates the effect of 1,25-dihydroxyvitamin D3 to induce growth arrest and differentiation of human myeloid leukemia cells via down-regulation of CYP24. Leuk Res 2006, 30(8):1005-1011.
38. Ikezoe T., Hisatake Y., Takeuchi T., Ohtsuki Y., Yang Y., Said J.W., et al. HIV-1 protease inhibitor, ritonavir: a potent inhibitor of CYP3A4, enhanced the anticancer effects of docetaxel in androgen-independent prostate cancer cells in vitro and in vivo. Cancer Res 2004, 64(20):7426-7431.
39. Mayor T. Navigating the ERAD interaction network. Nat Cell Biol 2011, 14(1):46-47.
40. Andre P., Groettrup M., Klenerman P., de G.R., Booth B.L., Cerundolo V., et al. An inhibitor of HIV-1 protease modulates proteasome activity, antigen presentation, and T cell responses. Proc Natl Acad Sci USA 1998, 95(22):13120-13124.
41. Britton M., Lucas M.M., Downey S.L., Screen M., Pletnev A.A., Verdoes M., et al. Selective inhibitor of proteasome's caspase-like sites sensitizes cells to specific inhibition of chymotrypsin-like sites. Chem Biol 2009, 16(12):1278-1289.
42. Gatti G., Di B.A., Casazza R., De P.C., Bassetti M., Cruciani M., et al. The relationship between ritonavir plasma levels and side-effects: implications for therapeutic drug monitoring. AIDS 1999, 13(15):2083-2089.