Targeting sphingolipid metabolism in head and neck cancer: Rational therapeutic potentials

Expert Opinion on Therapeutic Targets

Volumn 14, Issue 5, 2010, Pages 529-539

  Beckham, Thomas H ^a   Elojeimy, Saeed ^b   Cheng, Joseph C ^a   Turner, Lorianne S ^c   Hoffman, Stanley R ^d   Norris, James S ^a   Liu, Xiang ^a  

^a MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^b CAROLINAS MEDICAL CENTER   (United States)

^c FRANCIS MARION UNIVERSITY   (United States)

^d MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

Ceramide; Head and neck cancer; Lipid metabolism; Novel chemotherapeutic targets; Sphingolipids

Indexed keywords

2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; ANTINEOPLASTIC AGENT; CERAMIDE; CERAMIDE 1 PHOSPHATE; CERAMIDE GLUCOSYLTRANSFERASE; CH 11; CISPLATIN; DOXORUBICIN; ERYTHRO 2 (N MYRISTOYLAMINO) 1 PHENYL 1 PROPANOL; ETOPOSIDE; FINGOLIMOD; GEMCITABINE; IMIPRAMINE; LCL 204; LCL 385; SAFINGOL; SPHINGOLIPID; SPHINGOSINE 1 PHOSPHATE; SPHINGOSINE DERIVATIVE; SPHINGOSINE KINASE 1; SPHINGOSINE KINASE 1 INHIBITOR; UNCLASSIFIED DRUG;

CANCER INHIBITION; CHRONIC LYMPHATIC LEUKEMIA; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL; DRUG DOSE ESCALATION; DRUG MECHANISM; DRUG POTENTIATION; DRUG TARGETING; ENZYME INHIBITION; GRAFT REJECTION; HEAD AND NECK CANCER; HUMAN; LIPID METABOLISM; MULTIPLE MYELOMA; MULTIPLE SCLEROSIS; NONHUMAN; PROSTATE CANCER; REVIEW; SOLID TUMOR; TREATMENT RESPONSE;

HEAD AND NECK NEOPLASMS; HUMANS; SPHINGOLIPIDS;

EID: 77951106533     PISSN: 14728222     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728221003752768     Document Type: Review

References (98)

1. American Cancer Society: Cancer Facts and Figures 2009., Atlanta, 2009. Available from: http://www.cancer. org/downloads/STT/500809web.pdf [Last accessed 8 March 2010]
2. Day TA, Davis BK, Gillespie MB, et al. Oral cancer treatment. Curr Treat Options Oncol 2003;4:27-41
3. Futerman AH, Hannun YA. The complex life of simple sphingolipids. EMBO Rep 2004;5:777-782
4. Ogretmen B, Hannun YA. Biologically active sphingolipids in cancer pathogenesis and treatment. Nat Rev Cancer 2004;4:604-616
5. Hannun YA. Functions of ceramide in coordinating cellular responses to stress. Science 1996;274:1855-1859
6. Hannun YA, Luberto C. Ceramide in the eukaryotic stress response. Trends Cell Biol 2000;10:73-80
7. Hannun YA, Obeid LM. Ceramide: an intracellular signal for apoptosis. Trends Biochem Sci 1996;20:73-77
8. Mathias S, Pena LA, Kolesnick RN. Signal transduction of stress via ceramide. Biochem J 1998;335(Pt 3):465-480
9. Yao B, Zhang Y, Delikat S, et al. Phosphorylation of Raf by ceramide-activated protein kinase. Nature 1995;378:307-310
10. Chalfant CE, Rathman K, Pinkerman RL, et al. De novo ceramide regulates the alternative splicing of caspase 9 and Bcl-x in A549 lung adenocarcinoma cells. Dependence on protein phosphatase-1. J Biol Chem 2002;277:12587-12595
11. Dobrowsky RT, Hannun YA. Ceramide stimulates a cytosolic protein phosphatase. J Biol Chem 1992;267:5048-5051
12. Kashiwagi K, Shirai Y, Kuriyama M, et al. Importance of C1B domain for lipid messenger-induced targeting of protein kinase C. J Biol Chem 2002;277:18037-18045
13. Deiss LP, Galinka H, Berissi H, et al. Cathepsin D protease mediates programmed cell death induced by interferon-gamma, Fas/APO-1 and TNF-alpha. EMBO J 1996;15:3861-3870
14. Pattingre S, Bauvy C, Carpentier S, et al. Role of JNK1-dependent Bcl-2 phosphorylation in ceramide-induced macroautophagy. J Biol Chem 2009;284:2719-2728
15. Scarlatti F, Bauvy C, Ventruti A, et al. Ceramide-mediated macroautophagy involves inhibition of protein kinase B and up-regulation of beclin 1. J Biol Chem 2004;279:18384-18391
16. Daido S, Kanzawa T, Yamamoto A, et al. Pivotal role of the cell death factor BNIP3 in ceramide-induced autophagic cell death in malignant glioma cells. Cancer Res 2004;64:4286-4293
17. Xin M, Deng X. Protein phosphatase 2A enhances the proapoptotic function of Bax through dephosphorylation. J Biol Chem 2006;281:18859-18867
18. Lin SS, Bassik MC, Suh H, et al. PP2A regulates BCL-2 phosphorylation and proteasome-mediated degradation at the endoplasmic reticulum. J Biol Chem 2006;281:23003-23012
19. Reynolds CP, Maurer BJ, Kolesnick RN. Ceramide synthesis and metabolism as a target for cancer therapy. Cancer Lett 2004;206:169-180
20. Verheij M, van Blitterswijk WJ, Bartelink H. Radiation-induced apoptosis--the ceramide-SAPK signaling pathway and clinical aspects. Acta Oncol 1998;37:575-581
21. Nishina H, Wada T, Katada T. Physiological roles of SAPK/JNK signaling pathway. J Biochem 2004;136:123-126
22. Verheij M, Bose R, Lin XH, et al. Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis. Nature 1996;380:75-79
23. Kolesnick R. The therapeutic potential of modulating the ceramide/sphingomyelin pathway. J Clin Invest 2002;110:3-8
24. Huwiler A, Zangemeister-Wittke U. Targeting the conversion of ceramide to sphingosine 1-phosphate as a novel strategy for cancer therapy. Crit Rev Oncol Hematol 2007;63:150-159
25. Radin NS. Killing cancer cells by poly-drug elevation of ceramide levels: a hypothesis whose time has come? Eur J Biochem 2001;268:193-204
26. Saddoughi SA, Song P, Ogretmen B. Roles of bioactive sphingolipids in cancer biology and therapeutics. Subcell Biochem 2008;49:413-440
27. Hanada K, Kumagai K, Tomishige N, Yamaji T. CERT-mediated trafficking of ceramide. Biochim Biophys Acta 2009;1791:684-691
28. Swanton C, Marani M, Pardo O, et al. Regulators of mitotic arrest and ceramide metabolism are determinants of sensitivity to paclitaxel and other chemotherapeutic drugs. Cancer Cell 2007;11:498-512
29. Gouaze V, Yu JY, Bleicher RJ, et al. Overexpression of glucosylceramide synthase and P-glycoprotein in cancer cells selected for resistance to natural product chemotherapy. Mol Cancer Ther 2004;3:633-639
30. Liu Y-Y, Han T-Y, Giuliano AE, Cabot MC. Expression of glucosylceramide synthase, converting ceramide to glucosylceramide, confers adriamycin resistance in human breast cancer cells. J Biol Chem 1999;274:1140-1146
31. Liu YY, Han TY, Giuliano AE, Cabot MC. Ceramide glycosylation potentiates cellular multidrug resistance. FASEB J 2001;15:719-730
32. Chalfant CE, Ogretmen B, Galadari S, et al. FAS activation induces dephosphorylation of SR proteins; dependence on the de novo generation of ceramide and activation of protein phosphatase 1. J Biol Chem 2001;276:44848-44855
33. Liu Y-Y, Han TY, Yu JY, et al. Oligonucleotides blocking glucosylceramide synthase expression selectively reverse drug resistance in cancer cells. J Lipid Res 2004;45:933-940
34. Liu YY, Yu JY, Yin D, et al. A role for ceramide in driving cancer cell resistance to doxorubicin. FASEB J 2008;22:2541-2551
35. Weiss M, Hettmer S, Smith P, Ladisch S. Inhibition of melanoma tumor growth by a novel inhibitor of glucosylceramide synthase. Cancer Res 2003;63:3654-3658
36. Chalfant CE, Spiegel S. Sphingosine 1-phosphate and ceramide 1-phosphate: expanding roles in cell signaling. J Cell Sci 2005;118:4605-4612
37. Gomez-Munoz A, Kong JY, Parhar K, et al. Ceramide-1-phosphate promotes cell survival through activation of the phosphatidylinositol 3-kinase/protein kinase B pathway. FEBS Lett 2005;579:3744-3750
38. Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer 2009;9:550-562
39. Elojeimy S, Liu X, McKillop JC, 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
40. Kim WJ, Okimoto RA, Purton LE, et al. Mutations in the neutral sphingomyelinase gene SMPD3 implicate the ceramide pathway in human leukemias. Blood 2008;111:4716-4722
41. Ruckhaberle E, Rody A, Engels K, et al. Microarray analysis of altered sphingolipid metabolism reveals prognostic significance of sphingosine kinase 1 in breast cancer. Breast Cancer Res Treat 2008;112:41-52
42. Coward J, Ambrosini G, Musi E, et al. Safingol (L-threo-sphinganine) induces autophagy in solid tumor cells through inhibition of PKC and the PI3-kinase pathway. Autophagy 2009;5:184-193
43. Noda T, Iwai S, Hamada M, et al. Induction of apoptosis of detached oral squamous cell carcinoma cells by safingol. Possible role of Bim, focal adhesion kinase and endonuclease G. Apoptosis 2009;14:287-297
44. Senkal CE, Ponnusamy S, Rossi MJ, et al. Potent antitumor activity of a novel cationic pyridinium-ceramide alone or in combination with gemcitabine against human head and neck squamous cell carcinomas in vitro and in vivo. J Pharmacol Exp Ther 2006;317:1188-1199
45. Mahdy AE, Cheng JC, Li J, et al. Acid ceramidase upregulation in prostate cancer cells confers resistance to radiation: AC inhibition, a potential radiosensitizer. Mol Ther 2009;17:430-438
46. Grammatikos G, Teichgräber V, Carpinteiro A, et al. Overexpression of acid sphingomyelinase sensitizes glioma cells to chemotherapy. Antioxid Redox Signal 2007;9:1449-1456
47. Holman D, Turner LS, El-Zawahry A, et al. Lysosomotropic acid ceramidase inhibitor induces apoptosis in prostate cancer cells. Cancer Chemother Pharmacol 2008;61:231-242
48. Liu X, Elojeimy S, Stehouwer Turner L, et al. Implementation of acid ceramidase inhibitors as adjuncts to increase the efficacy of cancer therapy. In: Ochiai T, Shimada H, Tagawa M, editors, Gene Therapy 2007. 1st edition. 21st Century's Center of Excellence Program of Japanese Ministry of Education and Science: Chiba; 2007. p. 58-65
49. Saad AF, Meacham WD, Bai A, et al. The functional effects of acid ceramidase overexpression in prostate cancer progression and resistance to chemotherapy. Cancer Biol Ther 2007;6:1455-1460
50. French KJ, Upson JJ, Keller SN, et al. Antitumor activity of sphingosine kinase inhibitors. J Pharmacol Exp Ther 2006;318:596-603
51. Carvajal RD, Merrill AH Jr, Dials H, et al. A phase I clinical study of safingol followed by cisplatin: promising activity in refractory adrenocortical cancer with novel pharmacology. J Clin Oncol 2006;24:13044
52. Yuan Y, Chi F, Wang S, Wang Z. Significance of ceramide and DNA ploidy in laryngeal carcinogenesis. ORL J Otorhinolaryngol Relat Spec 2007;69:283-288
53. Chi FL, Yuan YS, Wang SY, Wang ZM. Study on ceramide expression and DNA content in patients with healthy mucosa, leukoplakia, and carcinoma of the larynx. Arch Otolaryngol Head Neck Surg 2004;130:307-310
54. Young MR, Neville BW, Chi AC, et al. Autocrine motility-stimulatory pathways of oral premalignant lesion cells. Clin Exp Metastasis 2007;24:131-139
55. Koybasi S, Senkal CE, Sundararaj K, et al. Defects in cell growth regulation by C18:0-ceramide and longevity assurance gene 1 in human head and neck squamous cell carcinomas. J Biol Chem 2004;279:44311-44319
56. Karahatay S, Thomas K, Koybasi S, et al. Clinical relevance of ceramide metabolism in the pathogenesis of human head and neck squamous cell carcinoma (HNSCC): attenuation of C18-ceramide in HNSCC tumors correlates with lymphovascular invasion and nodal metastasis. Cancer Lett 2007;256:101-111
57. Marques Filho MF, Walder F, Takahashi HK, et al. Glycosphingolipid expression in squamous cell carcinoma of the upper aerodigestive tract. Braz J Otorhinolaryngol 2006;72:25-30
58. Bolot G, David MJ, Taki T, et al. Analysis of glycosphingolipids of human head and neck carcinomas with comparison to normal tissue. Biochem Mol Biol Int 1998;46:125-135
59. Fish RG. Role of gangliosides in tumour progression: a molecular target for cancer therapy? Med Hypotheses 1996;46:140-144
60. Miller AV, Alvarez SE, Spiegel S, Lebman DA. Sphingosine kinases and sphingosine-1-phosphate are critical for transforming growth factor beta-induced extracellular signal-regulated kinase 1 and 2 activation and promotion of migration and invasion of esophageal cancer cells. Mol Cell Biol 2008;28:4142-4151
61. Bergelin N, Blom T, Heikkilä J, et al. Sphingosine kinase as an oncogene: autocrine sphingosine 1-phosphate modulates ML-1 thyroid carcinoma cell migration by a mechanism dependent on protein kinase C-alpha and ERK1/2. Endocrinology 2009;150:2055-2063
62. Senchenkov A, Litvak DA, Cabot MC. Targeting ceramide metabolism - a strategy for overcoming drug resistance. J Natl Cancer Inst 2001;93:347-357
63. Dumitru CA, Weller M, Gulbins E. Ceramide metabolism determines glioma cell resistance to chemotherapy. J Cell Physiol 2009;221:688-695
64. Rath G, Schneider C, Langlois B, et al. De novo ceramide synthesis is responsible for the anti-tumor properties of camptothecin and doxorubicin in follicular thyroid carcinoma. Int J Biochem Cell Biol 2009;41:1165-1172
65. Kolesnick R, Fuks Z. Radiation and ceramide-induced apoptosis. Oncogene 2003;22:5897-5906
66. Chmura SJ, Nodzenski E, Beckett MA, et al. Loss of ceramide production confers resistance to radiation-induced apoptosis. Cancer Res 1997;57:1270-1275
67. Chmura SJ, Nodzenski E, Kharbanda S, et al. Down-regulation of ceramide production abrogates ionizing radiation-induced cytochrome c release and apoptosis. Mol Pharmacol 2000;57:792-796
68. Alphonse G, Bionda C, Aloy MT, et al. Overcoming resistance to gamma-rays in squamous carcinoma cells by poly-drug elevation of ceramide levels. Oncogene 2004;23:2703-2715
69. Radin NS. Designing anticancer drugs via the achilles heel: ceramide, allylic ketones, and mitochondria. Bioorg Med Chem 2003;11:2123-2142
70. Stover TC, Sharma A, Robertson GP, Kester M. Systemic delivery of liposomal short-chain ceramide limits solid tumor growth in murine models of breast adenocarcinoma. Clin Cancer Res 2005;11:3465-3474
71. Shabbits JA, Mayer LD. Intracellular delivery of ceramide lipids via liposomes enhances apoptosis in vitro. Biochim Biophys Acta 2003;1612:98-106
72. Norris JS, Bielawska A, Day T, et al. Combined therapeutic use of AdGFPFasL and small molecule inhibitors of ceramide metabolism in prostate and head and neck cancers: a status report. Cancer Gene Ther 2006;13:1045-1051
73. Selzner M, Bielawska A, Morse MA, et al. Induction of apoptotic cell death and prevention of tumor growth by ceramide analogues in metastatic human colon cancer. Cancer Res 2001;61:1233-1240
74. Szulc ZM, Mayroo N, Bai A, et al. Novel analogs of D-e-MAPP and B13. Part 1: synthesis and evaluation as potential anticancer agents. Bioorg Med Chem 2008;16:1015-1031
75. Liu X, Elojeimy S, El-Zawahry AM, et al. Modulation of ceramide metabolism enhances viral protein apoptin's cytotoxicity in prostate cancer. Mol Ther 2006;14:637-646
76. Litvak DA, Bilchik AJ, Cabot MC. Modulators of ceramide metabolism sensitize colorectal cancer cells to chemotherapy: a novel treatment strategy. J Gastrointest Surg 2003;7:140-148; discussion 148
77. Kawamori T, Osta W, Johnson KR, et al. Sphingosine kinase 1 is up-regulated in colon carcinogenesis. FASEB J 2006;20:386-388
78. Taha TA, Kitatani K, El-Alwani M, et al. Loss of sphingosine kinase-1 activates the intrinsic pathway of programmed cell death: modulation of sphingolipid levels and the induction of apoptosis. FASEB J 2006;20:482-484
79. Van Brocklyn JR, Jackson CA, Pearl DK, et al. 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 2005;64:695-705
80. Barry JM, Lisa M, Carolyn B, et al. Synergistic cytotoxicity in solid tumor cell lines betwen N-(4-hydroxyphenyl) retinamide and modulators of ceramide metabolism. J Natl Cancer Inst 2000;92:1897
81. Hamada M, Sumi T, Iwai S, et al. Induction of endonuclease G-mediated apopotosis in human oral squamous cell carcinoma cells by protein kinase C inhibitor safingol. Apoptosis 2006;11:47-56
82. French KJ, Schrecengost RS, Lee BD, et al. Discovery and evaluation of inhibitors of human sphingosine kinase. Cancer Res 2003;63:5962-5969
83. Senkal CE, Ponnusamy S, Rossi MJ, et al. Role of human longevity assurance gene 1 and C18-ceramide in chemotherapy-induced cell death in human head and neck squamous cell carcinomas. Mol Cancer Ther 2007;6:712-722
84. Uchida T, Horiguchi S, Tanaka Y, et al. Phase I study of alpha-galactosylceramide-pulsed antigen presenting cells administration to the nasal submucosa in unresectable or recurrent head and neck cancer. Cancer Immunol Immunother 2008;57:337-345
85. Ishikawa A, Motohashi S, Ishikawa E, et al. A phase I study of alpha-galactosylceramide (KRN7000)-pulsed dendritic cells in patients with advanced and recurrent non-small cell lung cancer. Clin Cancer Res 2005;11:1910-1917
86. Visentin B, Vekich JA, Sibbald BJ, et al. Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages. Cancer Cell 2006;9:225-238
87. O'Brien N, Jones ST, Williams DG, et al. Production and characterization of monoclonal anti-sphingosine-1-phosphate antibodies. J Lipid Res 2009;50:2245-2257
88. Liu Q, Zhao X, Frissora F, et al. FTY720 demonstrates promising preclinical activity for chronic lymphocytic leukemia and lymphoblastic leukemia/lymphoma. Blood 2008;111:275-284
89. Lahiri S, Park H, Laviad EL, et al. Ceramide synthesis is modulated by the sphingosine analog FTY720 via a mixture of uncompetitive and noncompetitive inhibition in an Acyl-CoA chain length-dependent manner. J Biol Chem 2009;284:16090-16098
90. Berdyshev EV, Gorshkova I, Skobeleva A, et al. FTY720 inhibits ceramide synthases and up-regulates dihydrosphingosine 1-phosphate formation in human lung endothelial cells. J Biol Chem 2009;284:5467-5477
91. Neviani P, Santhanam R, Oaks JJ, et al. FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphocytic leukemia. J Clin Invest 2007;117:2408-2421
92. Yasui H, Hideshima T, Raje N, et al. FTY720 induces apoptosis in multiple myeloma cells and overcomes drug resistance. Cancer Res 2005;65:7478-7484
93. Salinas NR, Oshima CT, Cury PM, et al. FTY720 and lung tumor development. Int Immunopharmacol 2009;9:689-693
94. Shen Y, Wang X, Xia W, et al. Antiproliferative and overadditive effects of rapamycin and FTY720 in pancreatic cancer cells in vitro. Transplant Proc 2008;40:1727-1733
95. Shen Y, Cai M, Xia W, et al. FTY720, a synthetic compound from Isaria sinclairii, inhibits proliferation and induces apoptosis in pancreatic cancer cells. Cancer Lett 2007;254:288-297
96. Zhou C, Ling MT, Kin-Wah Lee T, et al. FTY720, a fungus metabolite, inhibits invasion ability of androgen-independent prostate cancer cells through inactivation of RhoA-GTPase. Cancer Lett 2006;233:36-47
97. Azuma H, Takahara S, Ichimaru N, et al. Marked prevention of tumor growth and metastasis by a novel immunosuppressive agent, FTY720, in mouse breast cancer models. Cancer Res 2002;62:1410-1419
98. Nagaoka Y, Otsuki K, Fujita T, Uesato S. Effects of phosphorylation of immunomodulatory agent FTY720 (fingolimod) on antiproliferative activity against breast and colon cancer cells. Biol Pharm Bull 2008 31:1177-1181