Sphingolipid-based drugs selectively kill cancer cells by down-regulating nutrient transporter proteins

Biochemical Journal

Volumn 439, Issue 2, 2011, Pages 299-311

  Romero Rosales, Kimberly ^a   Singh, Gurpreet ^a   Wu, Kevin ^a   Chen, Jie ^b   Janes, Matthew R ^c   Lilly, Michael B ^c   Peralta, Eigen R ^a   Siskind, Leah J ^d,e   Bennett, Michael J ^b   Fruman, David A ^c   Edinger, Aimee L ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d RALPH H JOHNSON VA MEDICAL CENTER   (United States)

^e MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

AAL 149; Autophagy; Bioenergetics; FTY720; Leukaemia; Nutrient limitation

Indexed keywords

BCR ABL PROTEIN; CARRIER PROTEIN; CERAMIDE; FINGOLIMOD; NUTRIENT TRANSPORTER PROTEIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; AUTOPHAGY; CANCER CELL; CELL MEMBRANE PERMEABILITY; CELL PROLIFERATION; CONTROLLED STUDY; DOWN REGULATION; DRUG MECHANISM; DRUG SELECTIVITY; DRUG SENSITIVITY; FEMALE; LEUKEMIA; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION;

ANIMALS; CARRIER PROTEINS; CELL LINE; DOWN-REGULATION; MICE; MICE, INBRED BALB C; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; SPHINGOLIPIDS; TANDEM MASS SPECTROMETRY;

ANIMALIA;

EID: 80053259864     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20110853     Document Type: Article

References (66)

1. vander Heiden, M. G., Cantley, L. C. and Thompson, C. B. (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324, 1029-1033
2. DeBerardinis, R. J., Lum, J. J., Hatzivassiliou, G. and Thompson, C. B. (2008) The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 7, 11-20
3. DeBerardinis, R. J., Mancuso, A., Daikhin, E., Nissim, I., Yudkoff, M., Wehrli, S. and Thompson, C. B. (2007) Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc. Natl. Acad. Sci. U.S.A. 104, 19345-19350
4. Yuneva, M., Zamboni, N., Oefner, P., Sachidanandam, R. and Lazebnik, Y. (2007) Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells. J. Cell Biol. 178, 93-105 (Pubitemid 47026405)
5. Mathew, R. and White, E. (2011) Autophagy in tumorigenesis and energy metabolism: friend by day, foe by night. Curr. Opin. Genet. Dev. 21, 113-119
6. Elstrom, R. L., Bauer, D. E., Buzzai, M., Karnauskas, R., Harris, M. H., Plas, D. R., Zhuang, H., Cinalli, R. M., Alavi, A., Rudin, C. M. and Thompson, C. B. (2004) Akt stimulates aerobic glycolysis in cancer cells. Cancer Res. 64, 3892-3899 (Pubitemid 38697301)
7. Yun, J., Rago, C., Cheong, I., Pagliarini, R., Angenendt, P., Rajagopalan, H., Schmidt, K., Willson, J. K., Markowitz, S., Zhou, S. et al. (2009) Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science 325, 1555-1559
8. Wise, D. R., DeBerardinis, R. J., Mancuso, A., Sayed, N., Zhang, X. Y., Pfeiffer, H. K., Nissim, I., Daikhin, E., Yudkoff, M., McMahon, S. B. and Thompson, C. B. (2008) Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc. Natl. Acad. Sci. U.S.A. 105, 18782-18787
9. Inoki, K., Zhu, T. and Guan, K. L. (2003) TSC2 mediates cellular energy response to control cell growth and survival. Cell 115, 577-590 (Pubitemid 37506046)
10. Shaw, R. J., Bardeesy, N., Manning, B. D., Lopez, L., Kosmatka, M., DePinho, R. A. and Cantley, L. C. (2004) The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell 6, 91-99 (Pubitemid 38903165)
11. Jones, R. G., Plas, D. R., Kubek, S., Buzzai, M., Mu, J., Xu, Y., Birnbaum, M. J. and Thompson, C. B. (2005) AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol. Cell 18, 283-293 (Pubitemid 41350534)
12. Matoba, S., Kang, J. G., Patino, W. D., Wragg, A., Boehm, M., Gavrilova, O., Hurley, P. J., Bunz, F. and Hwang, P. M. (2006) p53 regulates mitochondrial respiration. Science 312, 1650-1653 (Pubitemid 43902663)
13. Choo, A. Y., Kim, S. G., vander Heiden, M. G., Mahoney, S. J., Vu, H., Yoon, S. O., Cantley, L. C. and Blenis, J. (2010) Glucose addiction of TSC null cells is caused by failed mTORC1-dependent balancing of metabolic demand with supply. Mol. Cell 38, 487-499
14. Paez-Ribes, M., Allen, E., Hudock, J., Takeda, T., Okuyama, H., Vinals, F., Inoue, M., Bergers, G., Hanahan, D. and Casanovas, O. (2009) Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 15, 220-231
15. Ebos, J. M., Lee, C. R., Cruz-Munoz, W., Bjarnason, G. A., Christensen, J. G. and Kerbel, R. S. (2009) Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 15, 232-239
16. Narta, U. K., Kanwar, S. S. and Azmi, W. (2007) Pharmacological and clinical evaluation of L-asparaginase in the treatment of leukemia. Crit. Rev. Oncol. Hematol. 61, 208-221 (Pubitemid 46329425)
17. Kim, R. H., Coates, J. M., Bowles, T. L., McNerney, G. P., Sutcliffe, J., Jung, J. U., Gandour-Edwards, R., Chuang, F. Y., Bold, R. J. and Kung, H. J. (2009) Arginine deiminase as a novel therapy for prostate cancer induces autophagy and caspaseindependent apoptosis. Cancer Res. 69, 700-708
18. Guenther, G. G., Peralta, E. R., Rosales, K. R., Wong, S. Y., Siskind, L. J. and Edinger, A. L. (2008) Ceramide starves cells to death by downregulating nutrient transporter proteins. Proc. Natl. Acad. Sci. U.S.A. 105, 17402-17407
19. Lee, T. K., Man, K., Ho, J. W., Wang, X. H., Poon, R. T., Xu, Y., Ng, K. T., Chu, A. C., Sun, C. K., Ng, I. O. et al. (2005) FTY720: a promising agent for treatment of metastatic hepatocellular carcinoma. Clin. Cancer Res. 11, 8458-8466 (Pubitemid 41746961)
20. Azuma, H., Takahara, S., Ichimaru, N., Wang, J. D., Itoh, Y., Otsuki, Y., Morimoto, J., Fukui, R., Hoshiga, M., Ishihara, T. et al. (2002) Marked prevention of tumor growth and metastasis by a novel immunosuppressive agent, FTY720, in mouse breast cancer models. Cancer Res. 62, 1410-1419 (Pubitemid 34407800)
21. Chua, C. W., Lee, D. T., Ling, M. T., Zhou, C., Man, K., Ho, J., Chan, F. L., Wang, X. and Wong, Y. C. (2005) FTY720, a fungus metabolite, inhibits in vivo growth of androgen-independent prostate cancer. Int. J. Cancer 117, 1039-1048 (Pubitemid 41688582)
22. Azuma, H., Takahara, S., Horie, S., Muto, S., Otsuki, Y. and Katsuoka, Y. (2003) Induction of apoptosis in human bladder cancer cells in vitro and in vivo caused by FTY720 treatment. J. Urol. 169, 2372-2377 (Pubitemid 36576803)
23. Neviani, P., Santhanam, R., Oaks, J. J., Eiring, A. M., Notari, M., Blaser, B. W., Liu, S., Trotta, R., Muthusamy, N., Gambacorti-Passerini, C. et al. (2007) FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphocytic leukemia. J. Clin. Invest. 117, 2408-2421 (Pubitemid 47494343)
24. Yasui, H., Hideshima, T., Raje, N., Roccaro, A. M., Shiraishi, N., Kumar, S., Hamasaki, M., Ishitsuka, K., Tai, Y. T., Podar, K. et al. (2005) FTY720 induces apoptosis in multiple myeloma cells and overcomes drug resistance. Cancer Res. 65, 7478-7484 (Pubitemid 41161283)
25. Janes, M. R., Limon, J. J., So, L., Chen, J., Lim, R. J., Chavez, M. A., Vu, C., Lilly, M. B., Mallya, S., Ong, S. T. et al. (2010) Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor. Nat. Med. 16, 205-213
26. Manel, N., Kim, F. J., Kinet, S., Taylor, N., Sitbon, M. and Battini, J. L. (2003) The ubiquitous glucose transporter GLUT-1 is a receptor for HTLV. Cell 115, 449-459 (Pubitemid 37456807)
27. McKearn, J. P., McCubrey, J. and Fagg, B. (1985) Enrichment of hematopoietic precursor cells and cloning of multipotential B-lymphocyte precursors. Proc. Natl. Acad. Sci. U.S.A. 82, 7414-7418 (Pubitemid 16196830)
28. Welsch, C. A., Roth, L. W., Goetschy, J. F. and Movva, N. R. (2004) Genetic, biochemical, and transcriptional responses of Saccharomyces cerevisiae to the novel immunomodulator FTY720 largely mimic those of the natural sphingolipid phytosphingosine. J. Biol. Chem. 279, 36720-36731 (Pubitemid 39129019)
29. Deves, R. and Boyd, C. A. (2000) Surface antigen CD98(4F2): not a single membrane protein, but a family of proteins with multiple functions. J. Membr. Biol. 173, 165-177 (Pubitemid 30100209)
30. Verrey, F., Closs, E. I., Wagner, C. A., Palacin, M., Endou, H. and Kanai, Y. (2004) CATs and HATs: the SLC7 family of amino acid transporters. Pflügers Arch. 447, 532-542 (Pubitemid 38258215)
31. Eyster, C. A., Higginson, J. D., Huebner, R., Porat-Shliom, N., Weigert, R., Wu, W. W., Shen, R. F. and Donaldson, J. G. (2009) Discovery of new cargo proteins that enter cells through clathrin-independent endocytosis. Traffic 10, 590-599
32. Lu, X. and Silver, J. (2000) Ecotropic murine leukemia virus receptor is physically associated with caveolin and membrane rafts. Virology 276, 251-258
33. Mizushima, N., Levine, B., Cuervo, A. M. and Klionsky, D. J. (2008) Autophagy fights disease through cellular self-digestion. Nature 451, 1069-1075 (Pubitemid 351317450)
34. Jager, S., Bucci, C., Tanida, I., Ueno, T., Kominami, E., Saftig, P. and Eskelinen, E. L. (2004) Role for Rab7 in maturation of late autophagic vacuoles. J. Cell Sci. 117, 4837-4848 (Pubitemid 39433449)
35. Hardie, D. G. (2007) AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat. Rev. Mol. Cell. Biol. 8, 774-785
36. Wang, X. and Proud, C. G. (2009) Nutrient control of TORC1, a cell-cycle regulator. Trends Cell Biol. 19, 260-267
37. Rubin, D. and Ismail-Beigi, F. (2003) Distribution of Glut1 in detergent-resistant membranes (DRMs) and non-DRM domains: effect of treatment with azide. Am. J. Physiol. Cell Physiol. 285, C377-C383 (Pubitemid 36917852)
38. Zong, W. X., Ditsworth, D., Bauer, D. E., Wang, Z. Q. and Thompson, C. B. (2004) Alkylating DNA damage stimulates a regulated form of necrotic cell death. Genes Dev. 18, 1272-1282 (Pubitemid 38720595)
39. Pattingre, S., Tassa, A., Qu, X., Garuti, R., Liang, X. H., Mizushima, N., Packer, M., Schneider, M. D. and Levine, B. (2005) Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122, 927-939 (Pubitemid 41345209)
40. Wei, M. C., Zong, W. X., Cheng, E. H., Lindsten, T., Panoutsakopoulou, V., Ross, A. J., Roth, K. A., MacGregor, G. R., Thompson, C. B. and Korsmeyer, S. J. (2001) Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292, 727-730 (Pubitemid 32385543)
41. vander Heiden, M. G., Plas, D. R., Rathmell, J. C., Fox, C. J., Harris, M. H. and Thompson, C. B. (2001) Growth factors can influence cell growth and survival through effects on glucose metabolism. Mol. Cell. Biol. 21, 5899-5912 (Pubitemid 32737807)
42. Gems, D. and Partridge, L. (2008) Stress-response hormesis and aging: "that which does not kill us makes us stronger". Cell Metab. 7, 200-203 (Pubitemid 351285527)
43. Bauer, D. E., Harris, M. H., Plas, D. R., Lum, J. J., Hammerman, P. S., Rathmell, J. C., Riley, J. L. and Thompson, C. B. (2004) Cytokine stimulation of aerobic glycolysis in hematopoietic cells exceeds proliferative demand. FASEB J. 18, 1303-1305 (Pubitemid 39561584)
44. Edinger, A. L., Linardic, C. M., Chiang, G. G., Thompson, C. B. and Abraham, R. T. (2003) Differential effects of rapamycin on mammalian target of rapamycin signaling functions in mammalian cells. Cancer Res. 63, 8451-8460 (Pubitemid 37549501)
45. Bandhuvula, P., Tam, Y. Y., Oskouian, B. and Saba, J. D. (2005) The immune modulator FTY720 inhibits sphingosine-1-phosphate lyase activity. J. Biol. Chem. 280, 33697-33700 (Pubitemid 41443086)
46. Vessey, D. A., Kelley, M., Zhang, J., Li, L., Tao, R. and Karliner, J. S. (2007) Dimethylsphingosine and FTY720 inhibit the SK1 form but activate the SK2 form of sphingosine kinase from rat heart. J. Biochem. Mol. Toxicol. 21, 273-279 (Pubitemid 350006284)
47. Lahiri, S., Park, H., Laviad, E. L., Lu, X., Bittman, R. and Futerman, A. H. (2009) 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. 284, 16090-16098
48. Berdyshev, E. V., Gorshkova, I., Skobeleva, A., Bittman, R., Lu, X., Dudek, S. M., Mirzapoiazova, T., Garcia, J. G. and Natarajan, V. (2009) FTY720 inhibits ceramide synthases and up-regulates dihydrosphingosine 1-phosphate formation in human lung endothelial cells. J. Biol. Chem. 284, 5467-5477
49. Spassieva, S., Bielawski, J., Anelli, V. and Obeid, L. M. (2007) Combination of C17 sphingoid base homologues and mass spectrometry analysis as a new approach to study sphingolipid metabolism. Methods Enzymol. 434, 233-241
50. Siskind, L. J., Mullen, T. D., Romero Rosales, K., Clarke, C. J., Hernandez-Corbacho, M. J., Edinger, A. L. and Obeid, L. M. (2010) The BCL-2 protein BAK is required for long-chain ceramide generation during apoptosis. J. Biol. Chem. 285, 11818-11826
51. Rotmann, A., Strand, D., Martine, U. and Closs, E. I. (2004) Protein kinase C activation promotes the internalization of the human cationic amino acid transporter hCAT-1. A new regulatory mechanism for hCAT-1 activity. J. Biol. Chem. 279, 54185-54192 (Pubitemid 40053154)
52. Vina-Vilaseca, A., Bender-Sigel, J., Sorkina, T., Closs, E. I. and Sorkin, A. (2011) Protein kinase C-dependent ubiquitination and clathrin-mediated endocytosis of the cationic amino acid transporter CAT-1. J. Biol. Chem. 286, 8697-8706
53. Dobrowsky, R. T., Kamibayashi, C., Mumby, M. C. and Hannun, Y. A. (1993) Ceramide activates heterotrimeric protein phosphatase 2A. J. Biol. Chem. 268, 15523-15530 (Pubitemid 23222045)
54. Sanna, M. G., Liao, J., Jo, E., Alfonso, C., Ahn, M. Y., Peterson, M. S., Webb, B., Lefebvre, S., Chun, J., Gray, N. and Rosen, H. (2004) Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate. J. Biol. Chem. 279, 13839-13848 (Pubitemid 38468916)
55. Koyrakh, L., Roman, M. I., Brinkmann, V. and Wickman, K. (2005) The heart rate decrease caused by acute FTY720 administration is mediated by the G protein-gated potassium channel I. Am. J. Transplant. 5, 529-536 (Pubitemid 40313344)
56. Brinkmann, V. and Lynch, K. R. (2002) FTY720: targeting G-protein-coupled receptors for sphingosine 1-phosphate in transplantation and autoimmunity. Curr. Opin. Immunol. 14, 569-575
57. Sanchez, T. and Hla, T. (2004) Structural and functional characteristics of S1P receptors. J. Cell. Biochem. 92, 913-922 (Pubitemid 44264241)
58. Brinkmann, V., Davis, M. D., Heise, C. E., Albert, R., Cottens, S., Hof, R., Bruns, C., Prieschl, E., Baumruker, T., Hiestand, P. et al. (2002) The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J. Biol. Chem. 277, 21453-21457 (Pubitemid 34952287)
59. Butler, J., Lana, D., Round, O. and LaMontagne, K. (2004) Functional characterization of sphingosine 1-phosphate receptor agonist in human endothelial cells. Prostaglandins Other Lipid Mediators 73, 29-45 (Pubitemid 38446469)
60. Sensken, S. C., Bode, C. and Graler, M. H. (2009) Accumulation of fingolimod (FTY720) in lymphoid tissues contributes to prolonged efficacy. J. Pharmacol. Exp. Ther. 328, 963-969
61. Solomon, V. R. and Lee, H. (2009) Chloroquine and its analogs: a new promise of an old drug for effective and safe cancer therapies. Eur. J. Pharmacol. 625, 220-233
62. Tennant, D. A., Duran, R. V. and Gottlieb, E. (2010) Targeting metabolic transformation for cancer therapy. Nat. Rev. Cancer 10, 267-277
63. Schnabel, J. (2010) Targeting tumour metabolism. Nat. Rev. Drug Discovery 9, 503-504
64. Zeidan, Y. H., Jenkins, R. W. and Hannun, Y. A. (2008) Remodeling of cellular cytoskeleton by the acid sphingomyelinase/ceramide pathway. J. Cell Biol. 181, 335-350 (Pubitemid 351574557)
65. Donaldson, J. G. (2003) Multiple roles for Arf6: sorting, structuring, and signaling at the plasma membrane. J. Biol. Chem. 278, 41573-41576
66. Robertson, S. E., Setty, S. R., Sitaram, A., Marks, M. S., Lewis, R. E. and Chou, M. M. (2006) Extracellular signal-regulated kinase regulates clathrin-independent endosomal trafficking. Mol. Biol. Cell 17, 645-657 (Pubitemid 43191100)