96
Views
4
CrossRef citations to date
0
Altmetric
ORIGINAL ARTICLEPreclinical Therapeutics

Synthetic, Non-Natural Analogs of Ceramide Elevate Cellular Ceramide, Inducing Apoptotic Death to Prostate Cancer Cells and Eradicating Tumors in Mice

, , , &
Pages 535-543 | Published online: 16 Dec 2009

REFERENCES

  • Kolesnick, R.N.; Kronke, M. Regulation of ceramide production and apoptosis. Annu Rev Physiol 1998, 60, 643–665.
  • Perry, D.K. Ceramide and apoptosis. Biochem Soc Trans 1999, 27, 399–404.
  • Hannun, Y.A.; Luberto, C. Ceramide in the eukaryotic stress response. Trends Cell Biol 2000, 10, 73–80.
  • Toman, R.E.; Spiegel, S.; Faden, A.I. Role of ceramide in neuronal cell death and differentiation. J Neurotrauma 2000, 17, 891–898.
  • Jaffrezou, J.P.; Laurent, G.; Levade, T. Ceramide in regulation of apoptosis. Implication in multitoxicant resistance. Subcell Biochem 2002, 36, 269–284.
  • Hannun, Y.A.; Obeid, L.M. The Ceramide-centric universe of lipid-mediated cell regulation: stress encounters of the lipid kind. J Biol Chem 2002, 277, 25847–25850.
  • Ogretmen, B.; Hannun, Y.A. Biologically active sphingolipids in cancer pathogenesis and treatment. Nat Rev Cancer 2004, 4, 604–616.
  • Lowe, S.W.; Lin, A.W. Apoptosis in cancer. Carcinogenesis 2000, 21, 485–495.
  • 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.
  • Hannun, Y.A. Apoptosis and the dilemma of cancer chemotherapy. Blood 1997, 89, 1845–1853.
  • Ogura, M.; Handa, S. Induction of apoptosis by novel synthesized acylamides of human lymphocytes. Biochim Biophys Acta 2000, 1483, 111–118.
  • Mathias, S.; Pena, L.A.; Kolesnick, R.N. Signal transduction of stress via ceramide. Biochem J 1998, 335(Pt 3), 465–480.
  • 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.
  • Strum, J.C.; Small, G.W.; Pauig, S.B.; Daniel, L.W. 1-beta-D-Arabinofuranosylcytosine stimulates ceramide and diglyceride formation in HL-60 cells. J Biol Chem 1994, 269, 15493–15497.
  • 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.
  • Gill, J.S.; Windebank, A.J. Role of ceramide in suramin-induced cancer cell death. Cancer Lett 1997, 119, 169–176.
  • 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.
  • 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.
  • 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.
  • Kimura, K.; Bowen, C.; Spiegel, S.; Gelmann, E.P. Tumor necrosis factor-alpha sensitizes prostate cancer cells to gamma irradiation-induced apoptosis. Cancer Res 1999, 59, 1606–1614.
  • 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.
  • 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.
  • 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.
  • 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.
  • Kimura, K.; Markowski, M.; Bowen, C.; Gelmann, E.P. Androgen blocks apoptosis of hormone-dependent prostate cancer cells. Cancer Res 2001, 61, 5611–5618.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.