Inhibition of dihydroceramide desaturase activity by the sphingosine kinase inhibitor SKI II

Journal of Lipid Research

Volumn 55, Issue 8, 2014, Pages 1711-1720

  Cingolani, Francesca ^a   Casasampere, Mireia ^a   Sanllehí, Pol ^a,b   Casas, Josefina ^a   Bujons, Jordi ^a   Fabrias, Gemma ^a  

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

^b UNIVERSITY OF BARCELONA   (Spain)

Author keywords

Autophagy; Cell cycle; Enzyme inhibition; Mass spectrometry; Molecular docking; Reduced nicotinamide adenine dinucleotide cytochrome b5 reductase; Sphingolipids; Sphingosine kinase inhibitor II

Indexed keywords

CERAMIDE; CYTOCHROME B5 REDUCTASE; DIHYDROCERAMIDE; DIHYDROCERAMIDE DESATURASE; OXYGENASE; PHOSPHOTRANSFERASE INHIBITOR; SPHINGOSINE 1 PHOSPHATE; SPHINGOSINE KINASE INHIBITOR I; SPHINGOSINE KINASE INHIBITOR II; UNCLASSIFIED DRUG; ENZYME INHIBITOR; OXIDOREDUCTASE; PF-543; PHOSPHOTRANSFERASE; PYRROLIDINE DERIVATIVE; SPHINGOSINE KINASE; SPHINGOSINE KINASE 2, HUMAN; SULFONE;

ARTICLE; AUTOPHAGY; CELL CYCLE G0 PHASE; CELL CYCLE G1 PHASE; CELL LEVEL; CELL PROLIFERATION; COMPETITIVE INHIBITION; CONTROLLED STUDY; DRUG MECHANISM; DRUG SPECIFICITY; DRUG TARGETING; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; HUMAN CELL; LIPID STORAGE; MOLECULAR MODEL; PRIORITY JOURNAL; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; HELA CELL LINE; METABOLISM;

AUTOPHAGY; ENZYME INHIBITORS; G1 PHASE; HELA CELLS; HUMANS; OXIDOREDUCTASES; PHOSPHOTRANSFERASES (ALCOHOL GROUP ACCEPTOR); PYRROLIDINES; RESTING PHASE, CELL CYCLE; SULFONES;

EID: 84905057004     PISSN: 00222275     EISSN: 15397262     Source Type: Journal    
DOI: 10.1194/jlr.M049759     Document Type: Article

References (87)

1. Orr Gandy, K. A., and L. M. Obeid. 2013. Targeting the sphingosine kinase/sphingosine 1-phosphate pathway in disease: review of sphingosine kinase inhibitors. Biochim. Biophys. Acta. 1831: 157-166.
2. Heffernan-Stroud, L. A., and L. M. Obeid. 2013. Sphingosine kinase 1 in cancer. Adv. Cancer Res. 117: 201-235.
3. Alshaker, H., L. Sauer, D. Monteil, S. Ottaviani, S. Srivats, T. Böhler, and D. Pchejetski. 2013. Therapeutic potential of targeting SK1 in human cancers. Adv. Cancer Res. 117: 143-200.
4. Pyne, S., R. Bittman, and N. J. Pyne. 2011. Sphingosine kinase inhibitors and cancer: seeking the golden sword of Hercules. Cancer Res. 71: 6576-6582.
5. Zhang, Y., Y. Wang, Z. Wan, S. Liu, Y. Cao, and Z. Zeng. 2014. Sphingosine kinase 1 and cancer: a systematic review and meta-analysis. PLoS ONE. 9: e90362.
6. Neubauer, H. A., and S. M. Pitson. 2013. Roles, regulation and inhibitors of sphingosine kinase 2. FEBS J. 280: 5317-5336.
7. Lim, K. G., A. I. Gray, S. Pyne, and N. J. Pyne. 2012. Resveratrol dimers are novel sphingosine kinase 1 inhibitors and affect sphingosine kinase 1 expression and cancer cell growth and survival. Br. J. Pharmacol. 166: 1605-1616.
8. Schnute, M. E., M. D. McReynolds, T. Kasten, M. Yates, G. Jerome, J. W. Rains, T. Hall, J. Chrencik, M. Kraus, C. N. Cronin, et al. 2012. Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1. Biochem. J. 444: 79-88.
9. Gustin, D. J., Y. Li, M. L. Brown, X. Min, M. J. Schmitt, M. Wanska, X. Wang, R. Connors, S. Johnstone, M. Cardozo, et al. 2013. Structure guided design of a series of sphingosine kinase (SphK) inhibitors. Bioorg. Med. Chem. Lett. 23: 4608-4616.
10. Baek, D. J., N. MacRitchie, N. J. Pyne, S. Pyne, and R. Bittman. 2013. Synthesis of selective inhibitors of sphingosine kinase 1. Chem. Commun. (Camb.). 49: 2136-2138.
11. Byun, H-S., S. Pyne, N. MacRitchie, N. J. Pyne, and R. Bittman. 2013. Novel sphingosine-containing analogues selectively inhibit sphingosine kinase (SK) isozymes, induce SK1 proteasomal degradation and reduce DNA synthesis in human pulmonary arterial smooth muscle cells. Medchemcomm. 4: 1394-1399.
12. Raje, M. R., K. Knott, Y. Kharel, P. Bissel, K. R. Lynch, and W. L. Santos. 2012. Design, synthesis and biological activity of sphingosine kinase 2 selective inhibitors. Bioorg. Med. Chem. 20: 183-194.
13. Liu, K., T. L. Guo, N. C. Hait, J. Allegood, H. I. Parikh, W. Xu, G. E. Kellogg, S. Grant, S. Spiegel, and S. Zhang. 2013. Biological characterization of 3-(2-amino-ethyl)-5-[3-(4-butoxyl-phenyl)-propylidene]-thiazolidine-2,4-dione (K145) as a selective sphingosine kinase-2 inhibitor and anticancer agent. PLoS ONE. 8: e56471.
14. Wang, Z., X. Min, S-H. Xiao, S. Johnstone, W. Romanow, D. Meininger, H. Xu, J. Liu, J. Dai, S. An, et al. 2013. Molecular basis of sphingosine kinase 1 substrate recognition and catalysis. Structure. 21: 798-809.
15. Gao, P., Y. K. Peterson, R. A. Smith, and C. D. Smith. 2012. Characterization of isoenzyme-selective inhibitors of human sphingosine kinases. PLoS ONE. 7: e44543.
16. Yatomi, Y., F. Ruan, T. Megidish, T. Toyokuni, S. Hakomori, and Y. Igarashi. 1996. N,N-dimethylsphingosine inhibition of sphingosine kinase and sphingosine 1-phosphate activity in human platelets. Biochemistry. 35: 626-633. (Pubitemid 26032716)
17. Edsall, L. C., J. R. Van Brocklyn, O. Cuvillier, B. Kleuser, and S. Spiegel. 1998. N,N-Dimethylsphingosine is a potent competitive inhibitor of sphingosine kinase but not of protein kinase C: modulation of cellular levels of sphingosine 1-phosphate and ceramide. Biochemistry. 37: 12892-12898. (Pubitemid 28433522)
18. Olivera, A., T. Kohama, Z. Tu, S. Milstien, and S. Spiegel. 1998. Purification and characterization of rat kidney sphingosine kinase. J. Biol. Chem. 273: 12576-12583. (Pubitemid 28240634)
19. Maurer, B. J., L. Melton, C. Billups, M. C. Cabot, and C. P. Reynolds. 2000. Synergistic cytotoxicity in solid tumor cell lines between N-(4-hydroxyphenyl)retinamide and modulators of ceramide metabolism. J. Natl. Cancer Inst. 92: 1897-1909. (Pubitemid 32036920)
20. Kolesnick, R. 2002. The therapeutic potential of modulating the ceramide/sphingomyelin pathway. J. Clin. Invest. 110: 3-8. (Pubitemid 34743457)
21. Dickson, M. A., R. D. Carvajal, A. H. Merrill, M. Gonen, L. M. Cane, and G. K. Schwartz. 2011. A phase I clinical trial of safingol in combination with cisplatin in advanced solid tumors. Clin. Cancer Res. 17: 2484-2492.
22. Liu, H., M. Sugiura, V. E. Nava, L. C. Edsall, K. Kono, S. Poulton, S. Milstien, T. Kohama, and S. Spiegel. 2000. Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform. J. Biol. Chem. 275: 19513-19520. (Pubitemid 30441543)
23. Tonelli, F., K. G. Lim, C. Loveridge, J. Long, S. M. Pitson, G. Tigyi, R. Bittman, S. Pyne, and N. J. Pyne. 2010. FTY720 and (S)-FTY720 vinylphosphonate inhibit sphingosine kinase 1 and promote its proteasomal degradation in human pulmonary artery smooth muscle, breast cancer and androgen-independent prostate cancer cells. Cell. Signal. 22: 1536-1542.
24. Schwartz, G. K., J. Jiang, D. Kelsen, and A. P. Albino. 1993. Protein kinase C: a novel target for inhibiting gastric cancer cell invasion. J. Natl. Cancer Inst. 85: 402-407. (Pubitemid 23073160)
25. Igarashi, Y., S. Hakomori, T. Toyokuni, B. Dean, S. Fujita, M. Sugimoto, T. Ogawa, K. el-Ghendy, and E. Racker. 1989. Effect of chemically well-defined sphingosine and its N-methyl derivatives on protein kinase C and src kinase activities. Biochemistry. 28: 6796-6800. (Pubitemid 19219864)
26. Igarashi, Y., K. Kitamura, T. Toyokuni, B. Dean, B. Fenderson, T. Ogawass, and S. Hakomori. 1990. A specific enhancing effect of N,N-dimethylsphingosine on epidermal growth factor receptor autophosphorylation. Demonstration of its endogenous occurrence (and the virtual absence of unsubstituted sphingosine) in human epidermoid carcinoma A431 cells. J. Biol. Chem. 265: 5385-5389.
27. Sensken, S-C., and M. H. Gräler. 2010. Down-regulation of S1P1 receptor surface expression by protein kinase C inhibition. J. Biol. Chem. 285: 6298-6307.
28. Paugh, S. W., B. S. Paugh, M. Rahmani, D. Kapitonov, J. A. Almenara, T. Kordula, S. Milstien, J. K. Adams, R. E. Zipkin, S. Grant, et al. 2008. A selective sphingosine kinase 1 inhibitor integrates multiple molecular therapeutic targets in human leukemia. Blood. 112: 1382-1391.
29. Kapitonov, D., J. C. Allegood, C. Mitchell, N. C. Hait, J. A. Almenara, J. K. Adams, R. E. Zipkin, P. Dent, T. Kordula, S. Milstien, et al. 2009. Targeting sphingosine kinase 1 inhibits Akt signaling, induces apoptosis, and suppresses growth of human glioblastoma cells and xenografts. Cancer Res. 69: 6915-6923.
30. Hengst, J. A., X. Wang, U. H. Sk, A. K. Sharma, S. Amin, and J. K. Yun. 2010. Development of a sphingosine kinase 1 specific small-molecule inhibitor. Bioorg. Med. Chem. Lett. 20: 7498-7502.
31. French, K. J., R. S. Schrecengost, B. D. Lee, Y. Zhuang, S. N. Smith, J. L. Eberly, J. K. Yun, and C. D. Smith. 2003. Discovery and evaluation of inhibitors of human sphingosine kinase. Cancer Res. 63: 5962-5969. (Pubitemid 37187498)
32. Truman, J-P., M. García-Barros, L. M. Obeid, and Y. A. Hannun. Evolving concepts in cancer therapy through targeting sphingolipid metabolism. Biochim. Biophys. Acta. Epub ahead of print. December 30, 2013; doi:10.1016/j.bbalip.2013.12.013.
33. Lim, K. G., F. Tonelli, E. Berdyshev, I. Gorshkova, T. Leclercq, S. M. Pitson, R. Bittman, S. Pyne, and N. J. Pyne. 2012. Inhibition kinetics and regulation of sphingosine kinase 1 expression in prostate cancer cells: functional differences between sphingosine kinase 1a and 1b. Int. J. Biochem. Cell Biol. 44: 1457-1464.
34. Fabrias, G., J. Muñoz-Olaya, F. Cingolani, P. Signorelli, J. Casas, V. Gagliostro, and R. Ghidoni. 2012. Dihydroceramide desaturase and dihydrosphingolipids: debutant players in the sphingolipid arena. Prog. Lipid Res. 51: 82-94.
35. Kraveka, J. M., L. Li, Z. M. Szulc, J. Bielawski, B. Ogretmen, Y. A. Hannun, L. M. Obeid, and A. Bielawska. 2007. Involvement of dihydroceramide desaturase in cell cycle progression in human neuroblastoma cells. J. Biol. Chem. 282: 16718-16728. (Pubitemid 47093220)
36. Wang, H., B. J. Maurer, Y-Y. Liu, E. Wang, J. C. Allegood, S. Kelly, H. Symolon, Y. Liu, A. H. Merrill, V. Gouazé-Andersson, et al. 2008. N-(4-hydroxyphenyl)retinamide increases dihydroceramide and synergizes with dimethylsphingosine to enhance cancer cell killing. Mol. Cancer Ther. 7: 2967-2976.
37. Valsecchi, M., M. Aureli, L. Mauri, G. Illuzzi, V. Chigorno, A. Prinetti, and S. Sonnino. 2010. Sphingolipidomics of A2780 human ovarian carcinoma cells treated with synthetic retinoids. J. Lipid Res. 51: 1832-1840.
38. Illuzzi, G., C. Bernacchioni, M. Aureli, S. Prioni, G. Frera, C. Donati, M. Valsecchi, V. Chigorno, P. Bruni, S. Sonnino, et al. 2010. Sphingosine kinase mediates resistance to the synthetic retinoid N-(4-hydroxyphenyl)retinamide in human ovarian cancer cells. J. Biol. Chem. 285: 18594-18602.
39. Mao, Z., W. Sun, R. Xu, S. Novgorodov, Z. M. Szulc, J. Bielawski, L. M. Obeid, and C. Mao. 2010. Alkaline ceramidase 2 (ACER2) and its product dihydrosphingosine mediate the cytotoxicity of N-(4-hydroxyphenyl)retinamide in tumor cells. J. Biol. Chem. 285: 29078-29090.
40. Rahmaniyan, M., R. W. Curley, L. M. Obeid, Y. A. Hannun, and J. M. Kraveka. 2011. Identification of dihydroceramide desaturase as a direct in vitro target for fenretinide. J. Biol. Chem. 286: 24754-24764.
41. Apraiz, A., J. K. Idkowiak-Baldys, M. D. Boyano, G. Pérez-Yarza, Y. A. Hannun, and A. Asumendi. 2011. Evaluation of bioactive sphingolipids in 4-HPR-resistant leukemia cells. BMC Cancer. 11: 477.
42. Apraiz, A., J. Idkowiak-Baldys, N. Nieto-Rementería, M. D. Boyano, Y. A. Hannun, and A. Asumendi. 2012. Dihydroceramide accumulation and reactive oxygen species are distinct and nonessential events in 4-HPR-mediated leukemia cell death. Biochem. Cell Biol. 90: 209-223.
43. Bikman, B. T., Y. Guan, G. Shui, M. M. Siddique, W. L. Holland, J. Y. Kim, G. Fabriàs, M. R. Wenk, and S. A. Summers. 2012. Fenretinide prevents lipid-induced insulin resistance by blocking ceramide biosynthesis. J. Biol. Chem. 287: 17426-17437.
44. Yasuo, M., S. Mizuno, J. Allegood, D. Kraskauskas, H. J. Bogaard, S. Spiegel, and N. F. Voelkel. 2013. Fenretinide causes emphysema, which is prevented by sphingosine 1-phoshate. PLoS ONE. 8: e53927.
45. Zheng, W., J. Kollmeyer, H. Symolon, A. Momin, E. Munter, E. Wang, S. Kelly, J. C. Allegood, Y. Liu, Q. Peng, et al. 2006. Ceramides and other bioactive sphingolipid backbones in health and disease: lipidomic analysis, metabolism and roles in membrane structure, dynamics, signaling and autophagy. Biochim. Biophys. Acta. 1758: 1864-1884. (Pubitemid 44879367)
46. Holliday, M. W., S. B. Cox, M. H. Kang, and B. J. Maurer. 2013. C22:0- and C24:0-dihydroceramides confer mixed cytotoxicity in T-cell acute lymphoblastic leukemia cell lines. PLoS ONE. 8: e74768.
47. Munoz-Olaya, J. M., X. Matabosch, C. Bedia, M. Egido-Gabás, J. Casas, A. Llebaria, A. Delgado, and G. Fabriàs. 2008. Synthesis and biological activity of a novel inhibitor of dihydroceramide desaturase. ChemMedChem. 3: 946-953.
48. Bedia, C., J. Casas, N. Andrieu-Abadie, G. Fabriàs, and T. Levade. 2011. Acid ceramidase expression modulates the sensitivity of A375 melanoma cells to dacarbazine. J. Biol. Chem. 286: 28200-28209.
49. Schrödinger Suite 2013, Update 2. Schrödinger, LLC, New York, NY.
50. Maestro, version 9.5. Schrödinger, LLC, New York, NY.
51. MacroModel, version 10.1. Schrödinger, LLC, New York, NY.
52. Jorgensen, W. L., D. S. Maxwell, and J. Tirado-Rives. 1996. Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J. Am. Chem. Soc. 118: 11225-11236. (Pubitemid 26399746)
53. Still, W. C., A. Tempczyk, R. C. Hawley, and T. Hendrickson. 1990. Semianalytical treatment of solvation for molecular mechanics and dynamics. J. Am. Chem. Soc. 112: 6127-6129.
54. Bewley, M. C., C. C. Marohnic, and M. J. Barber. 2001. The structure and biochemistry of NADH-dependent cytochrome b5 reductase are now consistent. Biochemistry. 40: 13574-13582. (Pubitemid 33130785)
55. Berman, H. M., J. Westbrook, Z. Feng, G. Gilliland, T. N. Bhat, H. Weissig, I. N. Shindyalov, and P. E. Bourne. 2000. The Protein Data Bank. Nucleic Acids Res. 28: 235-242. (Pubitemid 30047768)
56. Schrödinger. Protein Preparation Wizard 2013-2; Epik version 2.4, Schrödinger, LLC, New York, NY. Impact version 5.9, Schrödinger, LLC, New York, NY. Prime version 3.2, Schrödinger, LLC, New York, NY.
57. Sastry, G. M., M. Adzhigirey, T. Day, R. Annabhimoju, and W. Sherman. 2013. Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J. Comput. Aided Mol. Des. 27: 221-234.
58. Olsson, M. H. M., C. R. Søndergard, M. Rostkowski, and J. H. Jensen. 2011. PROPKA3: Consistent treatment of internal and surface residues in empirical pKa predictions. J. Chem. Theory Comput. 7: 525-537.
59. Schrödinger. Induced Fit Docking protocol 2013-2, Glide version 5.9, Prime version 3.2. Schrödinger, LLC, New York, NY.
60. Sherman, W., T. Day, M. P. Jacobson, R. A. Friesner, and R. Farid. 2006. Novel procedure for modeling ligand/receptor induced fit effects. J. Med. Chem. 49: 534-553. (Pubitemid 43157487)
61. Sherman, W., H. S. Beard, and R. Farid. 2006. Use of an induced fit receptor structure in virtual screening. Chem. Biol. Drug Des. 67: 83-84. (Pubitemid 43881391)
62. Friesner, R. A., J. L. Banks, R. B. Murphy, T. A. Halgren, J. J. Klicic, D. T. Mainz, M. P. Repasky, E. H. Knoll, M. Shelley, J. K. Perry, et al. 2004. Glide: a new approach for rapid, accurate docking and scoring.1. Method and assessment of docking accuracy. J. Med. Chem. 47: 1739-1749. (Pubitemid 38380917)
63. Halgren, T. A., R. B. Murphy, R. A. Friesner, H. S. Beard, L. L. Frye, W. T. Pollard, and J. L. Banks. 2004. Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J. Med. Chem. 47: 1750-1759. (Pubitemid 38380918)
64. Prime, version 3.3. Schrödinger, LLC, New York, NY.
65. Loveridge, C., F. Tonelli, T. Leclercq, K. G. Lim, J. S. Long, E. Berdyshev, R. J. Tate, V. Natarajan, S. M. Pitson, N. J. Pyne, et al. 2010. The sphingosine kinase 1 inhibitor 2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole induces proteasomal degradation of sphingosine kinase 1 in mammalian cells. J. Biol. Chem. 285: 38841-38852.
66. Signorelli, P., J. M. Munoz-Olaya, V. Gagliostro, J. Casas, R. Ghidoni, and G. Fabriàs. 2009. Dihydroceramide intracellular increase in response to resveratrol treatment mediates autophagy in gastric cancer cells. Cancer Lett. 282: 238-243.
67. Çelik, H., and M. Koşar. 2012. Inhibitory effects of dietary flavonoids on purified hepatic NADH-cytochrome b5 reductase: structure-activity relationships. Chem. Biol. Interact. 197: 103-109.
68. Çelik, H., M. Koşar, and E. Arinç. 2013. In vitro effects of myricetin, morin, apigenin, (+)-taxifolin, (+)-catechin, (-)-epicatechin, naringenin and naringin on cytochrome b5 reduction by purified NADH-cytochrome b5 reductase. Toxicology. 308: 34-40.
69. Havsteen, B. H. 2002. The biochemistry and medical significance of the flavonoids. Pharmacol. Ther. 96: 67-202.
70. Verma, S., A. Singh, and A. Mishra. 2012. Molecular construction of NADH-cytochrome b5 reductase inhibition by flavonoids and chemical basis of difference in inhibition potential: molecular dynamics simulation study. J. Appl. Pharm. Sci. 2: 33-39.
71. Nishida, H., K. Inaka, M. Yamanaka, S. Kaida, K. Kobayashi, and K. Miki. 1995. Crystal structure of NADH-cytochrome b5 reductase from pig liver at 2.4 A resolution. Biochemistry. 34: 2763-2767.
72. Bando, S., T. Takano, T. Yubisui, K. Shirabe, M. Takeshita, and A. Nakagawa. 2004. Structure of human erythrocyte NADH-cytochrome b5 reductase. Acta Crystallogr. D Biol. Crystallogr. 60: 1929-1934. (Pubitemid 41087521)
73. Yamada, M., T. Tamada, K. Takeda, F. Matsumoto, H. Ohno, M. Kosugi, K. Takaba, Y. Shoyama, S. Kimura, R. Kuroki, et al. 2013. Elucidations of the catalytic cycle of NADH-cytochrome b5 reductase by X-ray crystallography: new insights into regulation of efficient electron transfer. J. Mol. Biol. 425: 4295-4306.
74. Triola, G., G. Fabriàs, J. Casas, and A. Llebaria. 2003. Synthesis of cyclopropene analogues of ceramide and their effect on dihydroceramide desaturase. J. Org. Chem. 68: 9924-9932. (Pubitemid 38017845)
75. Idkowiak-Baldys, J., A. Apraiz, L. Li, M. Rahmaniyan, C. J. Clarke, J. M. Kraveka, A. Asumendi, and Y. A. Hannun. 2010. Dihydroceramide desaturase activity is modulated by oxidative stress. Biochem. J. 427: 265-274.
76. Tonelli, F., M. Alossaimi, L. Williamson, R. J. Tate, D. G. Watson, E. Chan, R. Bittman, N. J. Pyne, and S. Pyne. 2013. The sphingosine kinase inhibitor 2-(p-hyroxyanilino)-4-(p-chlorophenyl)thiazole reduces androgen receptor expression via an oxidative stress-dependent mechanism. Br. J. Pharmacol. 168: 1497-1505.
77. Ricci, C., F. Onida, F. Servida, F. Radaelli, G. Saporiti, K. Todoerti, G. L. Deliliers, and R. Ghidoni. 2009. In vitro anti-leukaemia activity of sphingosine kinase inhibitor. Br. J. Haematol. 144: 350-357.
78. Kohno, M., M. Momoi, M. L. Oo, J-H. Paik, Y-M. Lee, K. Venkataraman, Y. Ai, A. P. Ristimaki, H. Fyrst, H. Sano, et al. 2006. Intracellular role for sphingosine kinase 1 in intestinal adenoma cell proliferation. Mol. Cell. Biol. 26: 7211-7223. (Pubitemid 44477697)
79. Taha, T. A., K. Kitatani, M. El-Alwani, J. Bielawski, Y. A. Hannun, and L. M. Obeid. 2006. Loss of sphingosine kinase-1 activates the intrinsic pathway of programmed cell death: modulation of sphingolipid levels and the induction of apoptosis. FASEB J. 20: 482-484. (Pubitemid 46671223)
80. Gao, P., and C. D. Smith. 2011. Ablation of sphingosine kinase-2 inhibits tumor cell proliferation and migration. Mol. Cancer Res. 9: 1509-1519.
81. Van Brocklyn, J. R., C. A. Jackson, D. K. Pearl, M. S. Kotur, P. J. Snyder, and T. W. Prior. 2005. Sphingosine kinase-1 expression correlates with poor survival of patients with glioblastoma multiforme: roles of sphingosine kinase isoforms in growth of glioblastoma cell lines. J. Neuropathol. Exp. Neurol. 64: 695-705.
82. Zhang, H., W. Li, S. Sun, S. Yu, M. Zhang, and F. Zou. 2012. Inhibition of sphingosine kinase 1 suppresses proliferation of glioma cells under hypoxia by attenuating activity of extracellular signal-regulated kinase. Cell Prolif. 45: 167-175.
83. Gagliostro, V., J. Casas, A. Caretti, J. L. Abad, L. Tagliavacca, R. Ghidoni, G. Fabrias, and P. Signorelli. 2012. Dihydroceramide delays cell cycle G1/S transition via activation of ER stress and induction of autophagy. Int. J. Biochem. Cell Biol. 44: 2135-2143.
84. Spassieva, S. D., M. Rahmaniyan, J. Bielawski, C. J. Clarke, J. M. Kraveka, and L. M. Obeid. 2012. Cell density-dependent reduction of dihydroceramide desaturase activity in neuroblastoma cells. J. Lipid Res. 53: 918-28.
85. Zhou, W., X-L. Ye, Z-J. Sun, X-D. Ji, H-X. Chen, and D. Xie. 2009. Overexpression of degenerative spermatocyte homolog 1 up-regulates the expression of cyclin D1 and enhances metastatic efficiency in esophageal carcinoma Eca109 cells. Mol. Carcinog. 48: 886-894.
86. Bedia, C., T. Levade, and P. Codogno. 2011. Regulation of autophagy by sphingolipids. Anticancer. Agents Med. Chem. 11: 844-853.
87. Beljanski, V., C. Knaak, and C. D. Smith. 2010. A novel sphingosine kinase inhibitor induces autophagy in tumor cells. J. Pharmacol. Exp. Ther. 333: 454-464.