Ceramidases in hematological malignancies: Senseless or neglected target?

Anti-Cancer Agents in Medicinal Chemistry

Volumn 11, Issue 9, 2011, Pages 830-843

  Fabriàs, Gemma ^a   Bedia, Carmen ^a   Casas, Josefina ^a   Abad, José Luis ^a   Delgado, Antonio ^a,b  

^a INSTITUTE OF ADVANCED CHEMISTRY OF CATALONIA IQAC CSIC   (Spain)

^b UNIVERSITY OF BARCELONA   (Spain)

Author keywords

Cancer; Ceramidase; Chemotherapy; Enzyme assay; Enzyme inhibitor; Sphingolipids

Indexed keywords

2 (4 ETHYL 1 PIPERAZINYL) 4 PHENYLQUINOLINE DIMALEATE; ACID CERAMIDASE INHIBITOR; ANTINEOPLASTIC AGENT; BORTEZOMIB; CERAMIDASE; CISPLATIN; DACINOSTAT; DASATINIB; DAUNORUBICIN; DESIPRAMINE; DM 102; DOXORUBICIN; ETOPOSIDE; GEMCITABINE; IMATINIB; INTERLEUKIN 1BETA; JANUS KINASE; LCL 204; LCL 385; N OLEOYLETHANOLAMINE; NILOTINIB; PROTEIN C JUN; RITUXIMAB; SORAFENIB; SPHINGOLIPID; STRESS ACTIVATED PROTEIN KINASE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; CELL PROLIFERATION; COLON ADENOCARCINOMA; CYTOTOXICITY; DNA DAMAGE; DRUG EFFICACY; DRUG POTENCY; DRUG SELECTIVITY; ENZYME ACTIVITY; ENZYME GLYCOSYLATION; ENZYME PHOSPHORYLATION; GLIOBLASTOMA; HEMATOLOGIC MALIGNANCY; HISTONE ACETYLATION; HUMAN; IC 50; IN VITRO STUDY; IN VIVO STUDY; LIPID METABOLISM; NEUROEPITHELIOMA; NONHUMAN; NONLYMPHATIC LEUKEMIA; OXIDATIVE STRESS; PROSTATE CANCER; PROTEIN CLEAVAGE; PROTEIN EXPRESSION; SOLID TUMOR; SQUAMOUS CELL CARCINOMA; TUMOR XENOGRAFT;

EID: 80054097990     PISSN: 18715206     EISSN: 18755992     Source Type: Journal    
DOI: 10.2174/187152011797655104     Document Type: Article

References (149)

1. Mao, C.; Obeid, L. M., Ceramidases: regulators of cellular responses mediated by ceramide, sphingosine, and sphingosine-1- phosphate. Biochim. Biophys. Acta, 2008, 1781 (9), 424-434.
2. Kono, M.; Dreier, J. L.; Ellis, J. M.; Allende, M. L.; Kalkofen, D. N.; Sanders, K. M.; Bielawski, J.; Bielawska, A.; Hannun, Y. A.; Proia, R. L., Neutral ceramidase encoded by the Asah2 gene is essential for the intestinal degradation of sphingolipids. J. Biol. Chem., 2006, 281 (11), 7324-7331.
3. Maltesen, H. R.; Troelsen, J. T.; Olsen, J., Identification of a functional hepatocyte nuclear factor 4 binding site in the neutral ceramidase promoter. J. Cell. Biochem., 2010, 111 (5), 1330-1336.
4. Sun, W.; Jin, J.; Xu, R.; Hu, W.; Szulc, Z. M.; Bielawski, J.; Obeid, L. M.; Mao, C., Substrate specificity, membrane topology, activity regulation of human alkaline ceramidase 2 (ACER2). J. Biol. Chem., 2010, 285 (12), 8995-9007.
5. Mao, C.; Xu, R.; Szulc, Z. M.; Bielawska, A.; Galadari, S. H.; Obeid, L. M., Cloning and characterization of a novel human alkaline ceramidase: a mammalian enzyme that hydrolyzes phytoceramide. J. Biol. Chem., 2001, 276 (28), 26577-26588.
6. Hu, W.; Xu, R.; Sun, W.; Szulc, Z. M.; Bielawski, J.; Obeid, L. M.; Mao, C., Alkaline ceramidase 3 (ACER3) hydrolyzes unsaturated long-chain ceramides, and its down-regulation inhibits both cell proliferation and apoptosis. J. Biol. Chem., 2010, 285 (11), 7964-7976.
7. Blachnio-Zabielska, A.; Zabielski, P.; Baranowski, M.; Gorski, J., Aerobic Training in Rats Increases Skeletal Muscle Sphingomyelinase and Serine Palmitoyltransferase Activity, While Decreasing Ceramidase Activity. Lipids, 2010, DOI 10.1007/s11745-11010- 13515-z.
8. Uchida, Y.; Houben, E.; Park, K.; Douangpanya, S.; Lee, Y. M.; Wu, B. X.; Hannun, Y. A.; Radin, N. S.; Elias, P. M.; Holleran, W. M., Hydrolytic Pathway Protects against Ceramide-Induced Apoptosis in Keratinocytes Exposed to UVB. J. Invest. Dermatol., 2010, 130 (10), 2472-2480.
9. Forster, A.; Emmler, T.; Schwalm, S.; Ebadi, M.; Heringdorf, D. M.; Nieuwenhuis, B.; Kleuser, B.; Huwiler, A.; Pfeilschifter, J., Glucocorticoids protect renal mesangial cells from apoptosis by increasing cellular sphingosine-1-phosphate. Kidney Int., 2010, 77 (10), 870-879.
10. Holland, W. L.; Miller, R. A.; Wang, Z. V.; Sun, K.; Barth, B. M.; Bui, H. H.; Davis, K. E.; Bikman, B. T.; Halberg, N.; Rutkowski, J. M.; Wade, M. R.; Tenorio, V. M.; Kuo, M. S.; Brozinick, J. T.; Zhang, B. B.; Birnbaum, M. J.; Summers, S. A.; Scherer, P. E., Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nat. Med., 2011, 17 (1), 55-63.
11. Eliyahu, E.; Shtraizent, N.; Martinuzzi, K.; Barritt, J.; He, X.; Wei, H.; Chaubal, S.; Copperman, A. B.; Schuchman, E. H., Acid ceramidase improves the quality of oocytes and embryos and the outcome of in vitro fertilization. FASEB J., 2009, 24 (4), 1229-1238.
12. Acharya, J. K.; Dasgupta, U.; Rawat, S. S.; Yuan, C.; Sanxaridis, P. D.; Yonamine, I.; Karim, P.; Nagashima, K.; Brodsky, M. H.; Tsunoda, S.; Acharya, U., Cell-nonautonomous function of ceramidase in photoreceptor homeostasis. Neuron, 2008, 57 (1), 69-79
13. Acharya, U.; Mowen, M. B.; Nagashima, K.; Acharya, J. K., Ceramidase expression facilitates membrane turnover and endocytosis of rhodopsin in photoreceptors. Proc. Natl. Acad. Sci. USA, 2004, 101 (7), 1922-1926
14. Acharya, U.; Patel, S.; Koundakjian, E.; Nagashima, K.; Han, X.; Acharya, J. K., Modulating sphingolipid biosynthetic pathway rescues photoreceptor degeneration. Science, 2003, 299 (5613), 1740-1743.
15. Rohrbough, J.; Rushton, E.; Palanker, L.; Woodruff, E.; Matthies, H. J.; Acharya, U.; Acharya, J. K.; Broadie, K., Ceramidase regulates synaptic vesicle exocytosis and trafficking. J. Neurosci., 2004, 24 (36), 7789-7803.
16. Yoshimura, Y.; Tani, M.; Okino, N.; Iida, H.; Ito, M., Molecular cloning and functional analysis of zebrafish neutral ceramidase. J. Biol. Chem., 2004, 279 (42), 44012-44022.
17. Delgado, A.; Casas, J.; Llebaria, A.; Abad, J. L.; Fabrias, G., Inhibitors of sphingolipid metabolism enzymes. Biochim. Biophys. Acta, 2006, 1758 (12), 1957-1977
18. Delgado, A.; Casas, J.; Llebaria, A.; Abad, J. L.; Fabrias, G., Chemical Tools to Investigate Sphingolipid Metabolism and Functions. ChemMedChem, 2007, 2 (5), 580-606.
19. Sugita, M.; Willians, M.; Dulaney, J. T.; Moser, H. W., Ceramidase and ceramide synthesis in human kidney and cerebellum. Description of a new alkaline ceramidase. Biochim. Biophys. Acta, 1975, 398 (1), 125-131.
20. Houben, E.; Uchida, Y.; Nieuwenhuizen, W. F.; De Paepe, K.; Vanhaecke, T.; Holleran, W. M.; Rogiers, V., Kinetic Characteristics of Acidic and Alkaline Ceramidase in Human Epidermis. Skin Pharmacol. Physiol., 2007, 20 (4), 187-194.
21. Spinedi, A.; Di Bartolomeo, S.; Piacentini, M., N-Oleoylethanolamine inhibits glucosylation of natural ceramides in CHP-100 neuroepithelioma cells: possible implications for apoptosis. Biochem. Biophys. Res. Commun., 1999, 255 (2), 456-459.
22. Chmura, S. J.; Nodzenski, E.; Kharbanda, S.; Pandey, P.; Quintans, J.; Kufe, D. W.; Weichselbaum, R. R., Down-regulation of ceramide production abrogates ionizing radiation-induced cytochrome c release and apoptosis. Mol. Pharmacol., 2000, 57 (4), 792-796.
23. 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 (3), 1233-1240.
24. 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 (1-3), 47-52.
25. 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 (4), 382-393.
26. 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 (21), 12646-12654.
27. Xu, R.; Sun, W.; Jin, J.; Obeid, L. M.; Mao, C., Role of alkaline ceramidases in the generation of sphingosine and its phosphate in erythrocytes. FASEB J., 2010, 24 (7), 2507-2515.
28. Choi, M. S.; Anderson, M. A.; Zhang, Z.; Zimonjic, D. B.; Popescu, N.; Mukherjee, A. B., Neutral ceramidase gene: role in regulating ceramide-induced apoptosis. Gene, 2003, 315, 113-122.
29. 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 (2), 1032-1045
30. 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 (2), 1032-1045.
31. 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 (2), 231-242.
32. 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.; Norris, J. S., Modulation of Ceramide Metabolism Enhances Viral Protein Apoptin's Cytotoxicity in Prostate Cancer. Mol. Ther., 2006, 14 (5), 637-646.
33. 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. TAD.; Dong, J. Y.; Bielawska, A.; Hannun, Y. A.; Norris, J. S., Role of Acid Ceramidase in Resistance to FasL: Therapeutic Approaches Based on Acid Ceramidase Inhibitors and FasL Gene Therapy. Mol. Ther., 2007, 15 (7), 1259-1263.
34. Granot, T.; Milhas, D.; Carpentier, S.; Dagan, A.; Segui, B.; Gatt, S.; Levade, T., Caspase-dependent and -independent cell death of Jurkat human leukemia cells induced by novel synthetic ceramide analogs. Leukemia, 2006, 20 (3), 392-399.
35. Elojeimy, S.; Holman, D. H.; Liu, X.; El-Zawahry, A.; Villani, M.; Cheng, J. C.; Mahdy, A.; Zeidan, Y.; Bielwaska, A.; Hannun, Y. A.; Norris, J. S., New insights on the use of desipramine as an inhibitor for acid ceramidase. FEBS Lett., 2006, 580 (19), 4751-4756.
36. Mahdy, A. E.; Cheng, J. C.; Li, J.; Elojeimy, S.; Meacham, W. D.; Turner, L. S.; Bai, A.; Gault, C. R.; McPherson, A. S.; Garcia, N.; Beckham, T. H.; Saad, A.; Bielawska, A.; Bielawski, J.; Hannun, Y. A.; Keane, T. E.; Taha, M. I.; Hammouda, H. M.; Norris, J. S.; Liu, X., Acid Ceramidase Upregulation in Prostate Cancer Cells Confers Resistance to Radiation: AC Inhibition, a Potential Radiosensitizer. Mol. Ther., 2008, 17 (3), 430-438.
37. Bai, A.; Szulc, Z. M.; Bielawski, J.; Mayroo, N.; Liu, X.; Norris, J.; Hannun, Y. A.; Bielawska, A., Synthesis and bioevaluation of omega-N-amino analogs of B13. Bioorg. Med. Chem., 2009, 17, 1840-1848.
38. 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 (3), 161-169.
39. Bedia, C.; Triola, G.; Casas, J.; Llebaria, A.; Fabrias, G., Analogs of the dihydroceramide desaturase inhibitor GT11 modified at the amide function: synthesis and biological activities. Org. Biomol. Chem., 2005, 3 (20), 3707-3712
40. Grijalvo, S.; Bedia, C.; Triola, G.; Casas, J.; Llebaria, A.; Teixido, J.; Rabal, O.; Levade, T.; Delgado, A.; Fabrias, G., Design, synthesis and activity as acid ceramidase inhibitors of 2-oxooctanoyl and Noleoylethanolamine analogues. Chem. Phys. Lipids, 2006, 144 (1), 69-84
41. Bedia, C.; Canals, D.; Matabosch, X.; Harrak, Y.; Casas, J.; Llebaria, A.; Delgado, A.; Fabrias, G., Cytotoxicity and acid ceramidase inhibitory activity of 2-substituted aminoethanol amides. Chem. Phys. Lipids, 2008, 156 (1-2), 33-40.
42. Abad, J. L.; Fabrias, G.; Casas, J.; Garrido, M.; Camacho, L.; Simbari, F.; Delgado, A. derivados de aminoetanol sustituidos en c2 y su uso como antitumorales. P201031642, 2010.
43. Gouazé-Andersson, V.; Flowers, M.; Karimia, R.; Fabriás, G.; Delgado, A.; Casas, J.; Cabot, M. C., Inhibition of acid ceramidase by a 2-substituted aminoethanol amide synergistically sensitizes prostate cancer cells to N-(4-hydroxyphenyl) retinamide. Prostate, 2011, 71 (10), 1064-1073.
44. Bar, J.; Linke, T.; Ferlinz, K.; Neumann, U.; Schuchman, E. H.; Sandhoff, K., Molecular analysis of acid ceramidase deficiency in patients with Farber disease. Hum. Mutat., 2001, 17 (3), 199-209
45. Ehlert, K.; Frosch, M.; Fehse, N.; Zander, A.; Roth, J.; Vormoor, J., Farber disease: clinical presentation, pathogenesis and a new approach to treatment. Pediatr. Rheumatol. Online J., 2007, 5 (1), 15.
46. Arikawa, J.; Ishibashi, M.; Kawashima, M.; Takagi, Y.; Ichikawa, Y.; Imokawa, G., Decreased levels of sphingosine, a natural antimicrobial agent, may be associated with vulnerability of the stratum corneum from patients with atopic dermatitis to colonization by Staphylococcus aureus. J. Invest. Dermatol., 2002, 119 (2), 433-439
47. Higuchi, K.; Hara, J.; Okamoto, R.; Kawashima, M.; Imokawa, G., The skin of atopic dermatitis patients contains a novel enzyme, glucosylceramide sphingomyelin deacylase, which cleaves the N-acyl linkage of sphingomyelin and glucosylceramide. Biochem. J., 2000, 350 (Pt 3), 747-756
48. Houben, E.; Hachem, J. P.; De Paepe, K.; Rogiers, V., Epidermal Ceramidase Activity Regulates Epidermal Desquamation via Stratum Corneum Acidification. Skin Pharmacol. Physiol., 2008, 21 (2), 111-118
49. Houben, E.; Holleran, W. M.; Yaginuma, T.; Mao, C.; Obeid, L. M.; Rogiers, V.; Takagi, Y.; Elias, P. M.; Uchida, Y., Differentiation-associated expression of ceramidase isoforms in cultured keratinocytes and epidermis. J. Lipid Res., 2006, 47 (5), 1063-1070
50. Kita, K.; Sueyoshi, N.; Okino, N.; Inagaki, M.; Ishida, H.; Kiso, M.; Imayama, S.; Nakamura, T.; Ito, M., Activation of bacterial ceramidase by anionic glycerophospholipids: possible involvement in ceramide hydrolysis on atopic skin by Pseudomonas ceramidase. Biochem. J., 2002, 362 (Pt 3), 619-626
51. Ohnishi, Y.; Okino, N.; Ito, M.; Imayama, S., Ceramidase activity in bacterial skin flora as a possible cause of ceramide deficiency in atopic dermatitis. Clin. Diagn. Lab. Immunol., 1999, 6 (1), 101-104
52. Raymond, A. A.; Gonzalez de Peredo, A.; Stella, A.; Ishida-Yamamoto, A.; Bouyssie, D.; Serre, G.; Monsarrat, B.; Simon, M., Lamellar bodies of human epidermis: proteomics characterization by high throughput mass spectrometry and possible involvement of CLIP-170 in their trafficking/secretion. Mol. Cell. Proteomics, 2008, 7 (11), 2151-2175.
53. Jiang, Y. J.; Uchida, Y.; Lu, B.; Kim, P.; Mao, C.; Akiyama, M.; Elias, P. M.; Holleran, W. M.; Grunfeld, C.; Feingold, K. R., Ceramide stimulates ABCA12 expression via peroxisome proliferator-activated receptor {delta} in human keratinocytes. J. Biol. Chem., 2009, 284 (28), 18942-18952.
54. Inoue, H.; Someno, T.; Kawada, M.; Ikeda, D., Citric acid inhibits a bacterial ceramidase and alleviates atopic dermatitis in an animal model. J. Antibiot., 2010, 63 (10), 611-613.
55. He, X.; Huang, Y.; Li, B.; Gong, C. X.; Schuchman, E. H., Deregulation of sphingolipid metabolism in Alzheimer's disease. Neurobiol. Aging, 2008, 31 (3), 398-408
56. Huang, Y.; Tanimukai, H.; Liu, F.; Iqbal, K.; Grundke-Iqbal, I.; Gong, C. X., Elevation of the level and activity of acid ceramidase in Alzheimer's disease brain. Eur. J. Neurosci., 2004, 20 (12), 3489-3497.
57. Grassme, H.; Becker, K. A.; Zhang, Y.; Gulbins, E., Ceramide in bacterial infections and cystic fibrosis. Biol. Chem., 2008, 389 (11), 1371-1379
58. Riethmuller, J.; Anthonysamy, J.; Serra, E.; Schwab, M.; Doring, G.; Gulbins, E., Therapeutic efficacy and safety of amitriptyline in patients with cystic fibrosis. Cell Physiol. Biochem., 2009, 24 (1-2), 65-72
59. Teichgraber, V.; Ulrich, M.; Endlich, N.; Riethmuller, J.; Wilker, B.; De Oliveira-Munding, C. C.; van Heeckeren, A. M.; Barr, M. L.; von Kurthy, G.; Schmid, K. W.; Weller, M.; Tummler, B.; Lang, F.; Grassme, H.; Doring, G.; Gulbins, E., Ceramide accumulation mediates inflammation, cell death and infection susceptibility in cystic fibrosis. Nat. Med., 2008, 14 (4), 382-391.
60. Zhang, D. X.; Fryer, R. M.; Hsu, A. K.; Zou, A. P.; Gross, G. J.; Campbell, W. B.; Li, P. L., Production and metabolism of ceramide in normal and ischemic-reperfused myocardium of rats. Basic Res. Cardiol., 2001, 96 (3), 267-274
61. El Alwani, M.; Usta, J.; Nemer, G.; El Sabban, M.; Nasser, M.; Bitar, H.; Souki, R.; Dbaibo, G. S.; Bitar, F. F., Regulation of the sphingolipid signaling pathways in the growing and hypoxic rat heart. Prostaglandins Other Lipid Mediat., 2005, 78 (1-4), 249-263.
62. Geoffroy, K.; Troncy, L.; Wiernsperger, N.; Lagarde, M.; Bawab, S. E., Glomerular proliferation during early stages of diabetic nephropathy is associated with local increase of sphingosine-1-phosphate levels. FEBS Lett., 2005, 579 (5), 1249-1254
63. Geoffroy, K.; Wiernsperger, N.; Lagarde, M.; El Bawab, S., Bimodal effect of advanced glycation end-products on mesangial cells proliferation is mediated by neutral ceramidase regulation and endogenous sphingolipids. J. Biol. Chem., 2004, 279 (33), 34343-34352
64. Zager, R. A.; Conrad, S.; Lochhead, K.; Sweeney, E. A.; Igarashi, Y.; Burkhart, K. M., Altered sphingomyelinase and ceramide expression in the setting of ischemic and nephrotoxic acute renal failure. Kidney Int., 1998, 53 (3), 573-582.
65. Zhu, Q.; Jin, J. F.; Shan, X. H.; Liu, C. P.; Mao, X. D.; Xu, K. F.; Liu, C., Chronic activation of neutral ceramidase protects betacells against cytokine induced apoptosis. Acta Pharmacol. Sin., 2008, 29 (5), 593-599
66. Zhu, Q.; Shan, X.; Miao, H.; Lu, Y.; Xu, J.; You, N.; Liu, C.; Liao, D. F.; Jin, J., Acute activation of acid ceramidase affects cytokine-induced cytotoxicity in rat islet betacells. FEBS Lett., 2009, 583 (12), 2136-2141
67. Straczkowski, M.; Kowalska, I.; Baranowski, M.; Nikolajuk, A.; Otziomek, E.; Zabielski, P.; Adamska, A.; Blachnio, A.; Gorski, J.; Gorska, M., Increased skeletal muscle ceramide level in men at risk of developing type 2 diabetes. Diabetologia, 2007, 50 (11), 2366-2373
68. Blachnio-Zabielska, A.; Zabielski, P.; Baranowski, M.; Gorski, J., Effects of Streptozotocin-induced Diabetes and Elevation of Plasma FFA on Ceramide Metabolism in Rat Skeletal Muscle. Horm. Metab. Res., 2009, 42 (1), 1-7
69. Chavez, J. A.; Holland, W. L.; Bar, J.; Sandhoff, K.; Summers, S. A., Acid ceramidase overexpression prevents the inhibitory effects of saturated fatty acids on insulin signaling. J. Biol. Chem., 2005, 280 (20), 20148-20153
70. Samad, F.; Hester, K. D.; Yang, G.; Hannun, Y. A.; Bielawski, J., Altered adipose and plasma sphingolipid metabolism in obesity: a potential mechanism for cardiovascular and metabolic risk. Diabetes, 2006, 55 (9), 2579-2587.
71. Guo, J.; Qian, Y.; Xi, X.; Hu, X.; Zhu, J.; Han, X., Blockage of ceramide metabolism exacerbates palmitate inhibition of proinsulin gene expression in pancreatic beta-cells. Mol. Cell. Biochem., 2010, 338 (1-2), 283-290.
72. Dhami, R.; He, X.; Schuchman, E. H., Acid sphingomyelinase deficiency attenuates bleomycin-induced lung inflammation and fibrosis in mice. Cell Physiol. Biochem., 2010, 26 (4-5), 749-760.
73. Abrahan, C. E.; Miranda, G. E.; Agnolazza, D. L.; Politi, L. E.; Rotstein, N. P., Synthesis of sphingosine is essential for oxidative stress-induced apoptosis of photoreceptors. Invest. Ophthalmol. Vis. Sci., 2010, 51 (2), 1171-1180.
74. Petrusca, D. N.; Gu, Y.; Adamowicz, J. J.; Rush, N. I.; Hubbard, W. C.; Smith, P. A.; Berdyshev, E. V.; Birukov, K. G.; Lee, C. H.; Tuder, R. M.; Twigg, H. L., 3rd; Vandivier, R. W.; Petrache, I., Sphingolipid-mediated inhibition of apoptotic cell clearance by alveolar macrophages. J. Biol. Chem., 2010, 285 (51), 40322-40332.
75. Duan, R. D.; Nilsson, A., Metabolism of sphingolipids in the gut and its relation to inflammation and cancer development. Prog. Lipid Res., 2009, 48 (1), 62-72
76. Liu, X.; Elojeimy, S.; Turner, L. S.; Mahdy, A. E.; Zeidan, Y. H.; Bielawska, A.; Bielawski, J.; Dong, J. Y.; El-Zawahry, A. M.; Guo, G. W.; Hannun, Y. A.; Holman, D. H.; Rubinchik, S., Acid ceramidase inhibition: a novel target for cancer therapy. Front. Biosci., 2008, 13, 2293-2298
77. Park, J. H.; Schuchman, E. H., Acid ceramidase and human disease. Biochim. Biophys. Acta, 2006, 1758 (12), 2133-2138
78. Zeidan, Y. H.; Jenkins, R. W.; Korman, J. B.; Liu, X.; Obeid, L. M.; Norris, J. S.; Hannun, Y. A., Molecular targeting of acid ceramidase: implications to cancer therapy. Curr. Drug Targets, 2008, 9 (8), 653-661.
79. Seelan, R. S.; Qian, C.; Yokomizo, A.; Bostwick, D. G.; Smith, D. I.; Liu, W., Human acid ceramidase is overexpressed but not mutated in prostate cancer. Genes. Chromosomes Cancer, 2000, 29 (2), 137-146
80. Shah, M. V.; Zhang, R.; Irby, R.; Kothapalli, R.; Liu, X.; Arrington, T.; Frank, B.; Lee, N. H.; Loughran, T. P., Jr., Molecular profiling of LGL leukemia reveals role of sphingolipid signaling in survival of cytotoxic lymphocytes. Blood, 2008, 112 (3), 770-781
81. Ruckhaberle, E.; Holtrich, U.; Engels, K.; Hanker, L.; Gatje, R.; Metzler, D.; Karn, T.; Kaufmann, M.; Rody, A., Acid ceramidase 1 expression correlates with a better prognosis in ERpositive breast cancer. Climacteric, 2009, 12 (6), 502-513
82. Ruckhaberle, E.; Karn, T.; Rody, A.; Hanker, L.; Gatje, R.; Metzler, D.; Holtrich, U.; Kaufmann, M., Gene expression of ceramide kinase, galactosyl ceramide synthase and ganglioside GD3 synthase is associated with prognosis in breast cancer. J. Cancer Res. Clin. Oncol., 2009
83. Saad, A. F.; Meacham, W. D.; Bai, A.; Anelli, V.; Elojeimy, S.; Mahdy, A. E.; Turner, L. S.; Cheng, J.; Bielawska, A.; Bielawski, J.; Keane, T. E.; Obeid, L. M.; Hannun, Y. A.; Norris, J. S.; Liu, X., The Functional Effects of Acid Ceramidase Overexpression in Prostate Cancer Progression and Resistance to Chemotherapy. Cancer Biol. Ther., 2007, 6 (9), 1455-1460.
84. Eto, M.; Bennouna, J.; Hunter, O. C.; Lotze, M. T.; Amoscato, A. A., Importance of C16 ceramide accumulation during apoptosis in prostate cancer cells. Int. J. Urol., 2006, 13 (2), 148-156.
85. Turner, L. S.; Cheng, J. C.; Beckham, T. H.; Keane, T. E.; Norris, J. S.; Liu, X., Autophagy is increased in prostate cancer cells overexpressing acid ceramidase and enhances resistance to C(6) ceramide. Prostate Cancer Prostatic Dis., 2011, 14 (1), 30-37.
86. Hara, S.; Nakashima, S.; Kiyono, T.; Sawada, M.; Yoshimura, S.; Iwama, T.; Banno, Y.; Shinoda, J.; Sakai, N., p53-Independent ceramide formation in human glioma cells during gammaradiation- induced apoptosis. Cell Death Differ., 2004, 11 (8), 853-861
87. Hara, S.; Nakashima, S.; Kiyono, T.; Sawada, M.; Yoshimura, S.; Iwama, T.; Sakai, N., Ceramide triggers caspase activation during gamma-radiation-induced apoptosis of human glioma cells lacking functional p53. Oncol. Rep., 2004, 12 (1), 119-123.
88. Morales, A.; Paris, R.; Villanueva, A.; Llacuna, L.; Garcia-Ruiz, C.; Fernandez-Checa, J. C., Pharmacological inhibition or small interfering RNA targeting acid ceramidase sensitizes hepatoma cells to chemotherapy and reduces tumor growth in vivo. Oncogene, 2006, 26 (6), 905-916.
89. Musumarra, G.; Barresi, V.; Condorelli, D. F.; Scire, S., A bioinformatic approach to the identification of candidate genes for the development of new cancer diagnostics. Biol. Chem., 2003, 384 (2), 321-327.
90. Ruckhaberle, E.; Rody, A.; Engels, K.; Gaetje, R.; von Minckwitz, G.; Schiffmann, S.; Grosch, S.; Geisslinger, G.; Holtrich, U.; Karn, T.; Kaufmann, M., Microarray analysis of altered sphingolipid metabolism reveals prognostic significance of sphingosine kinase 1 in breast cancer. Breast Cancer Res. Treat., 2007, 112 (1), 41-52.
91. Thon, L.; Mathieu, S.; Kabelitz, D.; Adam, D., The murine TRAIL receptor signals caspase-independent cell death through ceramide. Exp. Cell Res., 2006, 312 (19), 3808-3821.
92. Liu, Y.; He, J.; Xie, X.; Su, G.; Teitz-Tennenbaum, S.; Sabel, M. S.; Lubman, D. M., Serum autoantibody profiling using a natural glycoprotein microarray for the prognosis of early melanoma. J. Proteome Res., 2010, 9 (11), 6044-6051.
93. Wu, B. X.; Zeidan, Y. H.; Hannun, Y. A., Downregulation of neutral ceramidase by gemcitabine: Implications for cell cycle regulation. Biochim. Biophys. Acta, 2009, 1791 (8), 730-739.
94. Batra, S.; Reynolds, C. P.; Maurer, B. J., Fenretinide cytotoxicity for Ewing's sarcoma and primitive neuroectodermal tumor cell lines is decreased by hypoxia and synergistically enhanced by ceramide modulators. Cancer Res., 2004, 64 (15), 5415-5424
95. Noda, S.; Yoshimura, S.; Sawada, M.; Naganawa, T.; Iwama, T.; Nakashima, S.; Sakai, N., Role of ceramide during cisplatin-induced apoptosis in C6 glioma cells. J. Neurooncol., 2001, 52 (1), 11-21.
96. Mao, Z.; Sun, W.; Xu, R.; Novgorodov, S.; Szulc, Z. M.; Bielawski, J.; Obeid, L. M.; Mao, C., Alkaline ceramidase 2 (ACER2) and its product dihydrosphingosine mediate the cytotoxicity of 4-HPR in tumor cells. J. Biol. Chem., 2010, 285 (38), 29078-29090.
97. Furlong, S. J.; Ridgway, N. D.; Hoskin, D. W., Modulation of ceramide metabolism in T-leukemia cell lines potentiates apoptosis induced by the cationic antimicrobial peptide bovine lactoferricin. Int. J. Oncol., 2008, 32 (3), 537-544.
98. Thon, L.; Mohlig, H.; Mathieu, S.; Lange, A.; Bulanova, E.; Winoto-Morbach, S.; Schutze, S.; Bulfone-Paus, S.; Adam, D., Ceramide mediates caspase-independent programmed cell death. FASEB J., 2005, 19 (14), 1945-1956.
99. Ohta, H.; Sweeney, E. A.; Masamune, A.; Yatomi, Y.; Hakomori, S.; Igarashi, Y., Induction of apoptosis by sphingosine in human leukemic HL-60 cells: a possible endogenous modulator of apoptotic DNA fragmentation occurring during phorbol esterinduced differentiation. Cancer Res., 1995, 55 (3), 691-697.
100. Turzanski, J.; Grundy, M.; Russell, N. H.; Pallis, M., Interleukin- 1beta maintains an apoptosis-resistant phenotype in the blast cells of acute myeloid leukaemia via multiple pathways. Leukemia, 2004, 18 (10), 1662-1670.
101. Franzen, R.; Pautz, A.; Brautigam, L.; Geisslinger, G.; Pfeilschifter, J.; Huwiler, A., Interleukin-1beta induces chronic activation and de novo synthesis of neutral ceramidase in renal mesangial cells. J. Biol. Chem., 2001, 276 (38), 35382-35389.
102. Jaffrezou, J. P.; Levade, T.; Bettaieb, A.; Andrieu, N.; Bezombes, C.; Maestre, N.; Vermeersch, S.; Rousse, A.; Laurent, G., Daunorubicin-induced apoptosis: triggering of ceramide generation through sphingomyelin hydrolysis. EMBO J., 1996, 15 (10), 2417-2424.
103. Kolesnick, R. N.; Kronke, M., Regulation of ceramide production and apoptosis. Annu. Rev. Physiol., 1998, 60, 643-665.
104. Cuvillier, O., Sphingosine in apoptosis signaling. Biochim. Biophys. Acta, 2002, 1585 (2-3), 153-162.
105. Jarvis, W. D.; Fornari, F. A.; Traylor, R. S.; Martin, H. A.; Kramer, L. B.; Erukulla, R. K.; Bittman, R.; Grant, S., Induction of apoptosis and potentiation of ceramide-mediated cytotoxicity by sphingoid bases in human myeloid leukemia cells. J. Biol. Chem., 1996, 271 (14), 8275-8284
106. Ohta, H.; Yatomi, Y.; Sweeney, E. A.; Hakomori, S.; Igarashi, Y., A possible role of sphingosine in induction of apoptosis by tumor necrosis factor-alpha in human neutrophils. FEBS Lett., 1994, 355 (3), 267-270
107. Sweeney, E. A.; Inokuchi, J.; Igarashi, Y., Inhibition of sphingolipid induced apoptosis by caspase inhibitors indicates that sphingosine acts in an earlier part of the apoptotic pathway than ceramide. FEBS Lett., 1998, 425 (1), 61-65
108. Sweeney, E. A.; Sakakura, C.; Shirahama, T.; Masamune, A.; Ohta, H.; Hakomori, S.; Igarashi, Y., Sphingosine and its methylated derivative N,N-dimethylsphingosine (DMS) induce apoptosis in a variety of human cancer cell lines. Int. J. Cancer, 1996, 66 (3), 358-366.
109. Cuvillier, O.; Edsall, L.; Spiegel, S., Involvement of sphingosine in mitochondria-dependent Fas-induced apoptosis of type II Jurkat T cells. J. Biol. Chem., 2000, 275 (21), 15691-15700.
110. Krown, K. A.; Page, M. T.; Nguyen, C.; Zechner, D.; Gutierrez, V.; Comstock, K. L.; Glembotski, C. C.; Quintana, P. J.; Sabbadini, R. A., Tumor necrosis factor alpha-induced apoptosis in cardiac myocytes. Involvement of the sphingolipid signaling cascade in cardiac cell death. J. Clin. Invest., 1996, 98 (12), 2854-2865
111. Shirahama, T.; Sakakura, C.; Sweeney, E. A.; Ozawa, M.; Takemoto, M.; Nishiyama, K.; Ohi, Y.; Igarashi, Y., Sphingosine induces apoptosis in androgen-independent human prostatic carcinoma DU-145 cells by suppression of bcl-X(L) gene expression. FEBS Lett., 1997, 407 (1), 97-100
112. Hung, W. C.; Chang, H. C.; Chuang, L. Y., Activation of caspase-3-like proteases in apoptosis induced by sphingosine and other long-chain bases in Hep3B hepatoma cells. Biochem. J., 1999, 338 (Pt 1), 161-166.
113. Nica, A. F.; Tsao, C. C.; Watt, J. C.; Jiffar, T.; Kurinna, S.; Jurasz, P.; Konopleva, M.; Andreeff, M.; Radomski, M. W.; Ruvolo, P. P., Ceramide promotes apoptosis in chronic myelogenous leukemiaderived K562 cells by a mechanism involving caspase-8 and JNK. Cell Cycle, 2008, 7 (21), 3362-3370.
114. Jaffrezou, J. P.; Maestre, N.; Demasmansat, V.; Bezombes, C.; Levade, T.; Laurent, G., Positive feedback control of neutral sphingomyelinase activity by ceramide. FASEB J., 1998, 12 (11), 999-1006.
115. Ogretmen, B.; Pettus, B. J.; Rossi, M. J.; Wood, R.; Usta, J.; Szulc, Z.; Bielawska, A.; Obeid, L. M.; Hannun, Y. A., Biochemical mechanisms of the generation of endogenous long chain ceramide in response to exogenous short chain ceramide in the A549 human lung adenocarcinoma cell line: Role for endogenous ceramide in mediating the action of exogenous ceramide. J. Biol. Chem., 2002, 277 (15), 12960-12969.
116. Graf, C.; Rovina, P.; Bornancin, F., A secondary assay for ceramide kinase inhibitors based on cell growth inhibition by shortchain ceramides. Anal. Biochem., 2009, 384 (1), 166-169.
117. Segui, B.; Bezombes, C.; Uro-Coste, E.; Medin, J. A.; Andrieu- Abadie, N.; Auge, N.; Brouchet, A.; Laurent, G.; Salvayre, R.; Jaffrezou, J. P.; Levade, T., Stress-induced apoptosis is not mediated by endolysosomal ceramide. FASEB J., 2000, 14 (1), 36-47.
118. Burek, C.; Roth, J.; Koch, H. G.; Harzer, K.; Los, M.; Schulze- Osthoff, K., The role of ceramide in receptor- and stress-induced apoptosis studied in acidic ceramidase-deficient Farber disease cells. Oncogene, 2001, 20 (45), 6493-6502.
119. Ricci, C.; Onida, F.; Ghidoni, R., Sphingolipid players in the leukemia arena. Biochim. Biophys. Acta, 2006
120. Ekiz, H. A.; Baran, Y., Therapeutic applications of bioactive sphingolipids in hematological malignancies. Int. J. Cancer, 2010, 127 (7), 1497-1506.
121. Bezombes, C.; Laurent, G.; Jaffrezou, J. P., Implication of raft microdomains in drug induced apoptosis. Curr. Med. Chem. Anticancer Agents, 2003, 3 (4), 263-270.
122. Bose, R.; Verheij, M.; Haimovitz-Friedman, A.; Scotto, K.; Fuks, Z.; Kolesnick, R., Ceramide synthase mediates daunorubicininduced apoptosis: an alternative mechanism for generating death signals. Cell, 1995, 82 (3), 405-414.
123. Bezombes, C.; Grazide, S.; Garret, C.; Fabre, C.; Quillet-Mary, A.; Muller, S.; Jaffrezou, J. P.; Laurent, G., Rituximab Antiproliferative Effect in B Lymphoma Cells is Associated with Acid-Sphingomyelinase Activation in Raft Microdomains. Blood, 2004, 104 (4), 1166-1173.
124. Smith, M. A., Update on developmental therapeutics for acute lymphoblastic leukemia. Curr. Hematol. Malig. Rep., 2009, 4 (3), 175-182.
125. Maziere, C.; Conte, M. A.; Maziere, J. C., Activation of the JAK/STAT pathway by ceramide in cultured human fibroblasts. FEBS Lett., 2001, 507 (2), 163-168.
126. Kim, S.; Kim, Y.; Lee, Y.; Chung, J. H., Ceramide accelerates ultraviolet-induced MMP-1 expression through JAK1/STAT-1 pathway in cultured human dermal fibroblasts. J. Lipid Res., 2008, 49 (12), 2571-2581.
127. Shida, D.; Takabe, K.; Kapitonov, D.; Milstien, S.; Spiegel, S., Targeting SphK1 as a new strategy against cancer. Curr. Drug Targets, 2008, 9 (8), 662-673.
128. Drexler, H. G., Expression of FLT3 receptor and response to FLT3 ligand by leukemic cells. Leukemia, 1996, 10 (4), 588-599.
129. Maguer-Satta, V.; Oostendorp, R.; Reid, D.; Eaves, C. J., Evidence that ceramide mediates the ability of tumor necrosis factor to modulate primitive human hematopoietic cell fates. Blood, 2000, 96 (13), 4118-4123.
130. Park, M. A.; Zhang, G.; Martin, A. P.; Hamed, H.; Mitchell, C.; Hylemon, P. B.; Graf, M.; Rahmani, M.; Ryan, K.; Liu, X.; Spiegel, S.; Norris, J.; Fisher, P. B.; Grant, S.; Dent, P., Vorinostat and sorafenib increase ER stress, autophagy and apoptosis via ceramide-dependent CD95 and PERK activation. Cancer Biol. Ther., 2008, 7 (10), 1648-1662
131. Park, M. A.; Zhang, G.; Norris, J.; Hylemon, P. B.; Fisher, P. B.; Grant, S.; Dent, P., Regulation of autophagy by ceramide-CD95-PERK signaling. Autophagy, 2008, 4 (7), 929-931
132. Walker, T.; Mitchell, C.; Park, M. A.; Yacoub, A.; Graf, M.; Rahmani, M.; Houghton, P. J.; Voelkel-Johnson, C.; Grant, S.; Dent, P., Sorafenib and Vorinostat kill colon cancer cells by CD95-dependent and -independent mechanisms. Mol. Pharmacol., 2009, 76 (2), 342-355
133. Park, M. A.; Mitchell, C.; Zhang, G.; Yacoub, A.; Allegood, J.; Haussinger, D.; Reinehr, R.; Larner, A.; Spiegel, S.; Fisher, P. B.; Voelkel-Johnson, C.; Ogretmen, B.; Grant, S.; Dent, P., Vorinostat and Sorafenib Increase CD95 Activation in Gastrointestinal Tumor Cells through a Ca2+-De novo Ceramide-PP2A-Reactive Oxygen Species- Dependent Signaling Pathway. Cancer Res., 2010, 70 (15), 6313-6324.
134. Beljanski, V.; Knaak, C.; Smith, C. D., A novel sphingosine kinase inhibitor induces autophagy in tumor cells. J. Pharmacol. Exp. Ther., 2010, 333 (2), 454-464.
135. Pandolfi, P. P., Histone deacetylases and transcriptional therapy with their inhibitors. Cancer Chemother. Pharmacol., 2001, 48 Suppl 1, S17-S19
136. Rosato, R. R.; Grant, S., Histone deacetylase inhibitors: insights into mechanisms of lethality. Expert Opin. Ther. Targets, 2005, 9 (4), 809-824.
137. Wagner, J. M.; Hackanson, B.; Lubbert, M.; Jung, M., Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy. Clin. Epigenetics, 2010, 1 (3-4), 117-136.
138. Wooten-Blanks, L. G.; Song, P.; Senkal, C. E.; Ogretmen, B., Mechanisms of ceramide-mediated repression of the human telomerase reverse transcriptase promoter via deacetylation of Sp3 by histone deacetylase 1. FASEB J., 2007, 21 (12), 3386-3397.
139. Rosato, R. R.; Maggio, S. C.; Almenara, J. A.; Payne, S. G.; Atadja, P.; Spiegel, S.; Dent, P.; Grant, S., The Histone Deacetylase Inhibitor LAQ-824 Induces Human Leukemia Cell Death through a Process Involving XIAP Down-Regulation, Oxidative Injury, and the Acid Sphingomyelinase-Dependent Generation of Ceramide. Mol. Pharmacol., 2005, 69 (1), 216-225.
140. Rahmani, M.; Reese, E.; Dai, Y.; Bauer, C.; Payne, S. G.; Dent, P.; Spiegel, S.; Grant, S., Coadministration of histone deacetylase inhibitors and perifosine synergistically induces apoptosis in human leukemia cells through Akt and ERK1/2 inactivation and the generation of ceramide and reactive oxygen species. Cancer Res., 2005, 65 (6), 2422-2432.
141. Debret, R.; Brassart-Pasco, S.; Lorin, J.; Martoriati, A.; Deshorgue, A.; Maquart, F. X.; Hornebeck, W.; Rahman, I.; Antonicelli, F., Ceramide inhibition of MMP-2 expression and human cancer bronchial cell invasiveness involve decreased histone acetylation. Biochim. Biophys. Acta, 2008, 1783 (10), 1718-1727.
142. Hait, N. C.; Allegood, J.; Maceyka, M.; Strub, G. M.; Harikumar, K. B.; Singh, S. K.; Luo, C.; Marmorstein, R.; Kordula, T.; Milstien, S.; Spiegel, S., Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate. Science, 2009, 325 (5945), 1254-1257.
143. Bonhoure, E.; Lauret, A.; Barnes, D. J.; Martin, C.; Malavaud, B.; Kohama, T.; Melo, J. V.; Cuvillier, O., Sphingosine kinase-1 is a downstream regulator of imatinib-induced apoptosis in chronic myeloid leukemia cells. Leukemia, 2008, 22 (5), 971-979.
144. Baran, Y.; Salas, A.; Senkal, C. E.; Gunduz, U.; Bielawski, J.; Obeid, L. M.; Ogretmen, B., Alterations of ceramide/sphingosine- 1-phosphate rheostat involve in the regulation of resistance to imatinib-induced apoptosis in K562 human chronic myeloid leukemia (CML) cells. J. Biol. Chem., 2007, 282 (15), 10922-10934.
145. Nasr, R.; El-Sabban, M. E.; Karam, J. A.; Dbaibo, G.; Kfoury, Y.; Arnulf, B.; Lepelletier, Y.; Bex, F.; de The, H.; Hermine, O.; Bazarbachi, A., Efficacy and mechanism of action of the proteasome inhibitor PS-341 in T-cell lymphomas and HTLV-I associated adult T-cell leukemia/lymphoma. Oncogene, 2005, 24 (3), 419-430.
146. Franzen, R.; Fabbro, D.; Aschrafi, A.; Pfeilschifter, J.; Huwiler, A., Nitric oxide induces degradation of the neutral ceramidase in rat renal mesangial cells and is counterregulated by protein kinase C. J. Biol. Chem., 2002, 277 (48), 46184-46190
147. Franzen, R.; Pfeilschifter, J.; Huwiler, A., Nitric oxide induces neutral ceramidase degradation by the ubiquitin/proteasome complex in renal mesangial cell cultures. FEBS Lett., 2002, 532 (3), 441-444.
148. Jaffrezou, J. P.; Chen, G.; Duran, G. E.; Muller, C.; Bordier, C.; Laurent, G.; Sikic, B. I.; Levade, T., Inhibition of lysosomal acid sphingomyelinase by agents which reverse multidrug resistance. Biochim. Biophys. Acta, 1995, 1266 (1), 1-8.
149. Cloonan, S. M.; Drozgowska, A.; Fayne, D.; Williams, D. C., The antidepressants maprotiline and fluoxetine have potent selective antiproliferative effects against Burkitt lymphoma independently of the norepinephrine and serotonin transporters. Leuk. Lymphoma, 2010, 51 (3), 523-539.