Synthetic, non-natural analogs of ceramide elevate cellular ceramide, inducing apoptotic death to prostate cancer cells and eradicating tumors in mice

Cancer Investigation

Volumn 28, Issue 5, 2010, Pages 535-543

  Qin, Jing Dong ^a,d   Weiss, Lola ^b   Slavin, Shimon ^b,c   Gatt, Shimon ^a   Dagan, Arie ^a,b  

^a HEBREW UNIVERSITY   (Israel)

^b HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^c TEL AVIV SOURASKY MEDICAL CENTER   (Israel)

^d UNIVERSITY OF CHICAGO   (United States)

Author keywords

Apoptosis; Cancer; Ceramide; Prostate; Sphingolipids

Indexed keywords

2 (4 ETHYL 1 PIPERAZINYL) 4 PHENYLQUINOLINE DIMALEATE; 2 (N TETRADECYLAMINO) 3 PHENYL 3 PROPANOL; AD 2725; CERAMIDE; CERAMIDE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BAGG ALBINO MOUSE; CANCER CELL; CARCINOGENESIS; CONTROLLED STUDY; CYTOTOXICITY; ERADICATION THERAPY; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MALE; MOUSE; NONHUMAN; NONOBESE DIABETIC MOUSE; NUDE MOUSE; PRIORITY JOURNAL; PROSTATE CANCER; SCID MOUSE; SOLID TUMOR; TUMOR REGRESSION;

ANIMALS; APOPTOSIS; CELL LINE, TUMOR; CERAMIDES; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; MALE; MICE; MICE, INBRED BALB C; MICE, NUDE; MICE, SCID; NEOPLASM TRANSPLANTATION; PROSTATIC NEOPLASMS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 77952154130     PISSN: 07357907     EISSN: 15324192     Source Type: Journal    
DOI: 10.3109/07357900903478915     Document Type: Article

References (43)

1. Kolesnick, R.N.; Kronke, M. Regulation of ceramide production and apoptosis. Annu Rev Physiol 1998, 60, 643-665.
2. Perry, D.K. Ceramide and apoptosis. Biochem Soc Trans 1999, 27, 399-404.
3. Hannun, Y.A.; Luberto, C. Ceramide in the eukaryotic stress response. Trends Cell Biol 2000, 10, 73-80.
4. Toman, R.E.; Spiegel, S.; Faden, A.I. Role of ceramide in neuronal cell death and differentiation. J Neurotrauma 2000, 17, 891-898.
5. Jaffrezou, J.P.; Laurent, G.; Levade, T. Ceramide in regulation of apoptosis. Implication in multitoxicant resistance. Subcell Biochem 2002, 36, 269-284.
6. Hannun, Y.A.; Obeid, L.M. The Ceramide-centric universe of lipidmediated cell regulation: stress encounters of the lipid kind. J Biol Chem 2002, 277, 25847-25850.
7. Ogretmen, B.; Hannun, Y.A. Biologically active sphingolipids in cancer pathogenesis and treatment. Nat Rev Cancer 2004, 4, 604-616.
8. Lowe, S.W.; Lin, A.W. Apoptosis in cancer. Carcinogenesis 2000, 21, 485-495.
9. Herr, I.; Wilhelm, D.; Bohler, T.; Angel, P.; Debatin, K.M. Activation of CD95 (APO-1/Fas) signaling by ceramide mediates cancer therapy-induced apoptosis. Embo J 1997, 16, 6200-6208.
10. Hannun, Y.A. Apoptosis and the dilemma of cancer chemotherapy. Blood 1997, 89, 1845-1853.
11. Ogura, M.; Handa, S. Induction of apoptosis by novel synthesized acylamides of human lymphocytes. Biochim Biophys Acta 2000, 1483, 111-118.
12. Mathias, S.; Pena, L.A.; Kolesnick, R.N. Signal transduction of stress via ceramide. Biochem J 1998, 335(Pt 3), 465-480.
13. Maurer, B.J.; Metelitsa, L.S.; Seeger, R.C.; Cabot, M.C.; Reynolds, C.P. Increase of ceramide and induction of mixed apoptosis/ necrosis by N-(4-hydroxyphenyl)- retinamide in neuroblastoma cell lines. J Natl Cancer Inst 1999, 91, 1138-1146.
14. Strum, J.C.; Small, G.W.; Pauig, S.B.; Daniel, L.W. 1-beta- DArabinofuranosylcytosine stimulates ceramide and diglyceride formation in HL-60 cells. J Biol Chem 1994, 269, 15493-15497.
15. Cabot, M.C.; Giuliano, A.E.; Volner, A.; Han, T.Y. Tamoxifen retards glycosphingolipid metabolism in human cancer cells. FEBS Lett 1996, 394, 129-131.
16. Gill, J.S.; Windebank, A.J. Role of ceramide in suramin-induced cancer cell death. Cancer Lett 1997, 119, 169-176.
17. von Holtz, R.L.; Fink, C.S.; Awad, A.B. beta-Sitosterol activates the sphingomyelin cycle and induces apoptosis in LNCaP human prostate cancer cells. Nutr Cancer 1998, 32, 8-12.
18. Garzotto, M.; White-Jones, M.; Jiang, Y.; Ehleiter, D.; Liao, W.C.; Haimovitz-Friedman, A.; Fuks, Z.; Kolesnick, R. 12- O-tetradecanoylphorbol-13- acetate-induced apoptosis in LNCaP cells is mediated through ceramide synthase. Cancer Res 1998, 58, 2260-2264.
19. Garzotto, M.; Haimovitz-Friedman, A.; Liao, W.C.; White-Jones, M.; Huryk, R.; Heston, W.D.; Cardon-Cardo, C.; Kolesnick, R.; Fuks, Z. Reversal of radiation resistance in LNCaP cells by targeting apoptosis through ceramide synthase. Cancer Res 1999, 59, 5194-5201.
20. Kimura, K.; Bowen, C.; Spiegel, S.; Gelmann, E.P. Tumor necrosis factor-alpha sensitizes prostate cancer cells to gamma irradiationinduced apoptosis. Cancer Res 1999, 59, 1606-1614.
21. Nava, V.E.; Cuvillier, O.; Edsall, L.C.; Kimura, K.; Milstien, S.; Gelmann, E.P.; Spiegel, S. Sphingosine enhances apoptosis of radiation-resistant prostate cancer cells. Cancer Res 2000, 60, 4468-4474.
22. Wang, X.Z.; Beebe, J.R.; Pwiti, L.; Bielawska, A.; Smyth, M.J. Aberrant sphingolipid signaling is involved in the resistance of prostate cancer cell lines to chemotherapy. Cancer Res 1999, 59, 5842-5848.
23. Condorelli, F.; Canonico, P.L.; Sortino, M.A. Distinct effects of ceramide-generating pathways in prostate adenocarcinoma cells. Br J Pharmacol 1999, 127, 75-84.
24. Seelan, R.S.; Qian, C.; Yokomizo, A.; Bostwick, D.G.; Smith, D.I.; Liu, W. Human acid ceramidase is over expressed but not mutated in prostate cancer. Genes Chromosomes Can 2000, 29, 137-146.
25. Kimura, K.; Markowski, M.; Bowen, C.; Gelmann, E.P. Androgen blocks apoptosis of hormone-dependent prostate cancer cells. Cancer Res 2001, 61, 5611-5618.
26. Kimura, K.; Markowski, M.; Edsall, L.C.; Spiegel, S.; Gelmann, E.P. Role of ceramide in mediating apoptosis of irradiated LNCaP prostate cancer cells. Cell Death Differ 2003, 10, 240-248.
27. Eto, M.; Bennouna, J.; Hunter, O.C.; Hershberger, P.A.; Kanto, T.; Johnson, C.S.; Lotze, M.T.; Amoscato, A.A. C16 ceramide accumulates following androgen ablation in LNCaP prostate cancer cells. Prostate 2003, 57, 66-79.
28. Mimeault, M.; Pommery, N.; Wattez, N.; Bailly, C.; Henichart, J.P. Anti-proliferative and apoptotic effects of anandamide in human prostatic cancer cell lines: implication of epidermal growth factor receptor downregulation and ceramide production. Prostate 2003, 56, 1-12. (Pubitemid 36613150)
29. Mimeault, M.; Pommery, N.; Henichart, J.P. Synergistic antiproliferative and apoptotic effects induced by epidermal growth factor receptor and protein kinase a inhibitors in human prostatic cancer cell lines. Int J Cancer 2003, 106, 116-124. (Pubitemid 36750397)
30. Sala, G.; Minutolo, F.; Macchia, M.; Sacchi, N.; Ghidoni, R. Resveratrol structure and ceramide-associated growth inhibition in prostate cancer cells. Drugs Exp Clin Res 2003, 29, 263-269.
31. Wang, H.; Charles, A.G.; Frankel, A.J.; Cabot, M.C. Increasing intracellular ceramide: an approach that enhances the cytotoxic response in prostate cancer cells. Urology 2003, 61, 1047-1052.
32. Lim, S.; Ryu, J.H.; Im, C.; Yim, C.B. Synthesis and cytotoxicity of new 3-alkyl-1-(1-methyl-2-phenylethyl) ureas related to ceramide. Arch Pharm Res 2003, 26, 270-274.
33. Samsel, L.; Zaidel, G.; Drumgoole, H.M.; Jelovac, D.; Drachenberg, C.; Rhee, J.G.; Brodie, A.M.; Bielawska, A.; Smyth, M.J. The ceramide analog, B13, induces apoptosis in prostate cancer cell lines and inhibits tumor growth in prostate cancer xenografts. Prostate 2004, 58, 382-393.
34. Bielawska, A.; Greenberg, M.S.; Perry, D.; Jayadev, S.; Shayman, J.A.; McKay, C.; Hannun, Y.A. (1S,2R)-D-erythro-2- (N-myristoylamino)-1-phenyl-1- propanol as an inhibitor of ceramidase. J Biol Chem 1996, 271, 12646-12654.
35. Raisova, M.; Goltz, G.; Bektas, M.; Bielawska, A.; Riebeling, C.; Hossini, A.M.; Eberle, J.; Hannun, Y.A.; Orfanos, C.E.; Geilen, C.C. Bcl-2 overexpression prevents apoptosis induced by ceramidase inhibitors in malignant melanoma and HaCaT keratinocytes. FEBS Lett 2002, 516, 47-52.
36. Selzner, M.; Bielawska, A.; Morse, M.A.; Rudiger, H.A.; Sindram, D.; Hannun, Y.A.; Clavien, P.A. Induction of apoptotic cell death and prevention of tumor growth by ceramide analogues in metastatic human colon cancer. Cancer Res 2001, 61, 1233-1240.
37. Dagan, A.; Wang, C.; Fibach, E.; Gatt, S. Synthetic, non-natural sphingolipid analogs inhibit the biosynthesis of cellular sphingolipids, elevate ceramide and induce apoptotic cell death. Biochim Biophys Acta 2003, 1633, 161-169.
38. He, X.; Dagan, A.; Gatt, S.; Schuchman, E.H. Simultaneous quantitative analysis of ceramide and sphingosine in mouse blood by naphthalene-2,3- dicarboxyaldehyde derivatization after hydrolysis with ceramidase. Anal Biochem 2005, 340, 113-122.
39. Liu, X.; Elojeimy, S.; El-Zawahry, A.M.; Holman, D.H.; Bielawska, A.; Bielawski, J.; Rubinchik, S.; Guo, G.W.; Dong, J.Y.; Keane, T.; Hannun, Y.A.; Tavassoli, M.; et al. Modulation of ceramide metabolism enhances viral protein apoptin's cytotoxicity in prostate cancer. Mol Ther 2006, 14, 637-646.
40. Holman, D.H.; Turner, L.S.; El-Zawahry, A.; Elojeimy, S.; Liu, X.; Bielawski, J.; Szulc, Z.M.; Norris, K.; Zeidan, Y.H.; Hannun, Y.A.; Bielawska, A.; Norris, J.S. Lysosomotropic acid ceramidase inhibitor induces apoptosis in prostate cancer cells. Cancer Chemother Pharmacol 2008, 61, 231-242.
41. Elojeimy, S.; Liu, X.; McKillop, J.C.; El-Zawahry, A.M.; Holman, D.H.; Cheng, J.Y.; Meacham, W.D.; Mahdy, A.E.; Saad, A.F.; Turner, L.S.; Cheng, J.; Day, T.A.; et al. Role of acid ceramidase in resistance to FasL: therapeutic approaches based on acid ceramidase inhibitors and FasL gene therapy. Mol Ther 2007, 15, 1259-1263.
42. Szulc, Z.M.; Mayroo, N.; Bai, A.; Bielawski, J.; Liu, X.; Norris, J.S.; Hannun, Y.A.; Bielawska, A. Novel analogs of D-e-MAPP and B13. Part 1: synthesis and evaluation as potential anticancer agents. Bioorg Med Chem 2008, 16, 1015-1031.
43. Bielawska, A.; Bielawski, J.; Szulc, Z.M.; Mayroo, N.; Liu, X.; Bai, A.; Elojeimy, S.; Rembiesa, B.; Pierce, J.; Norris, J.S.; Hannun, Y.A. Novel analogs of D-e-MAPP and B13. Part 2: signature effects on bioactive sphingolipids. Bioorg Med Chem 2008, 16, 1032-1045. (Pubitemid 351163040)