Mitochondrially targeted ceramide LCL-30 inhibits colorectal cancer in mice

British Journal of Cancer

Volumn 98, Issue 1, 2008, Pages 98-105

  Dahm, F ^a   Bielawska, A ^b   Nocito, A ^a   Georgiev, P ^a   Szulc, Z M ^b   Bielawski, J ^b   Jochum, W ^a   Dindo, D ^a   Hannun, Y A ^b   Clavien, P A ^a  

^a UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^b MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

Cell death; Ceramides; Ceramidoids; Colorectal neoplasms; Drug therapy; Pharmacokinetics

Indexed keywords

2 N [16' (1'' PYRIDINIUM)HEXADECANOYL]SPHINGOSINE BROMIDE; ADENOSINE TRIPHOSPHATE; CERAMIDE; DACTINOMYCIN; DOXORUBICIN; LCL 30; SPHINGOLIPID; SPHINGOSINE 1 PHOSPHATE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER CELL CULTURE; CELL DEATH; CELL DIFFERENTIATION; CELL GROWTH; COLORECTAL CANCER; COMBINATION CHEMOTHERAPY; CONTROLLED STUDY; DRUG ABSORPTION; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG SAFETY; GENETIC TRANSCRIPTION; HISTOPATHOLOGY; IN VIVO STUDY; METASTASIS; MITOCHONDRION; MONOTHERAPY; MOUSE; NONHUMAN; PERITONEAL CAVITY; PRIORITY JOURNAL; SINGLE DRUG DOSE;

ANIMALS; APOPTOSIS; CASPASES; CELL PROLIFERATION; CELLS, CULTURED; CERAMIDES; COLORECTAL NEOPLASMS; CYTOCHROMES C; ENZYME-LINKED IMMUNOSORBENT ASSAY; HUMANS; MICE; MICE, INBRED BALB C; MITOCHONDRIA; MOLECULAR STRUCTURE; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SPHINGOLIPIDS; SPHINGOSINE; SURVIVAL RATE; TUMOR CELLS, CULTURED;

EID: 38049009070     PISSN: 00070920     EISSN: 15321827     Source Type: Journal    
DOI: 10.1038/sj.bjc.6604099     Document Type: Article

References (30)

1. Bielawski J, Szulc ZM, Hannun YA, Bielawska A (2006) Simultaneous quantitative analysis of bioactive sphingolipids by high-performance liquid chromatography-tandem mass spectrometry. Methods 39: 82-91
2. Birbes H, El Bawab S, Hannun YA, Obeid LM (2001) Selective hydrolysis of a mitochondrial pool of sphingomyelin induces apoptosis. FASEB J 15: 2669-2679
3. Bose R, Verheij M, Haimovitz-Friedman A, Scotto K, Fuks Z, Kolesnick R (1995) Ceramide synthase mediates daunorubicin-induced apoptosis: an alternative mechanism for generating death signals. Cell 82: 405-414
4. Bras A, Albar JP, Leonardo E, de Buitrago GG, Martinez AC (2000) Ceramide-induced cell death is independent of the Fas/Fas ligand pathway and is prevented by Nur77 overexpression in A20 B cells. Cell Death Differ 7: 262-271
5. Chen LB (1988) Mitochondrial membrane potential in living cells. Annu Rev Cell Biol 4: 155-181
6. Dahm F, Nocito A, Bielawska A, Lang KS, Georgiev P, Asmis LM, Bielawski J, Madon J, Hannun YA, Clavien PA (2006) Distribution and dynamic changes of sphingolipids in blood in response to platelet activation. J Thromb Haemost 4: 2704-2709
7. Di Paola M, Cocco T, Lorusso M (2000) Ceramide interaction with the respiratory chain of heart mitochondria. Biochemistry 39: 6660-6668
8. Dindo D, Dahm F, Szulc Z, Bielawska A, Obeid LM, Hannun YA, Graf R, Clavien P-A (2006) Cationic long-chain ceramide LCL-30 induces cell death by mitochondrial targeting in SW403 cells. Mol Cancer Ther 5: 1520-1529
9. Dubois V, Dasnois L, Lebtahi K, Collot F, Heylen N, Havaux N, Fernandez AM, Lobl TJ, Oliyai C, Nieder M, Shochat D, Yarranton GT, Trouet A (2002) CPI-0004Na, a new extracellularly tumor-activated prodrug of doxorubicin: in vivo toxicity, activity, and tissue distribution confirm tumor cell selectivity. Cancer Res 62: 2327-2331
10. El-Assaad W, Kozhaya L, Araysi S, Panjarian S, Bitar FF, Baz E, El-Sabban ME, Dbaibo GS (2003) Ceramide and glutathione define two independently regulated pathways of cell death initiated by p53 in Molt-4 leukaemia cells. Biochem J 376: 725-732
11. Fukuda Y, Kihara A, Igarashi Y (2003) Distribution of sphingosine kinase activity in mouse tissues: contribution of SPHK1. Biochem Biophys Res Commun 309: 155-160
12. Futerman AH, Hannun YA (2004) The complex life of simple sphingolipids. EMBO Rep 5: 777-782
13. Garcia-Ruiz C, Colell A, Mari M, Morales A, Fernandez-Checa JC (1997) Direct effect of ceramide on the mitochondrial electron transport chain leads to generation of reactive oxygen species. Role of mitochondrial glutathione. J Biol Chem 272: 11369-11377
14. Ghafourifar P, Klein SD, Schucht O, Schenk U, Pruschy M, Rocha S, Richter C (1999) Ceramide induces cytochrome c release from isolated mitochondria. Importance of mitochondrial redox state. J Biol Chem 274: 6080-6084
15. Ikeda H, Satoh H, Yanase M, Inoue Y, Tomiya T, Arai M, Tejima K, Nagashima K, Maekawa H, Yahagi N, Yatomi Y, Sakurada S, Takuwa Y, Ogata I, Kimura S, Fujiwara K (2003) Antiproliferative property of sphingosine 1-phosphate in rat hepatocytes involves activation of Rho via Edg-5. Gastroenterology 124: 459-469
16. Itoh M, Kitano T, Watanabe M, Kondo T, Yabu T, Taguchi Y, Iwai K, Tashima M, Uchiyama T, Okazaki T (2003) Possible role of ceramide as an indicator of chemoresistance: decrease of the ceramide content via activation of glucosylceramide synthase and sphingomyelin synthase in chemoresistant leukemia. Clin Cancer Res 9: 415-423
17. Liu H, Toman RE, Goparaju SK, Maceyka M, Nava VE, Sankala H, Payne SG, Bektas M, Ishii I, Chun J, Milstien S, Spiegel S (2003) Sphingosine kinase type 2 is a putative BH3-only protein that induces apoptosis. J Biol Chem 278: 40330-40336
18. Novgorodov SA, Szulc ZM, Luberto C, Jones JA, Bielawski J, Bielawska A, Hannun YA, Obeid LM (2005) Positively charged ceramide is a potent inducer of mitochondrial permeabilization. J Biol Chem 280: 16096-16105
19. Obeid LM, Linardic CM, Karolak LA, Hannun YA (1993) Programmed cell death induced by ceramide. Science 259: 1769-1771
20. Oh WJ, Kim WH, Kang KH, Kim TY, Kim MY, Choi KH (1998) Induction of p21 during ceramide-mediated apoptosis in human hepatocarcinoma cells. Cancer Lett 129: 215-222
21. Oskouian B, Sooriyakumaran P, Borowsky AD, Crans A, Dillard-Telm L, Tam YY, Bandhuvula P, Saba JD (2006) Sphingosine-1-phosphate lyase potentiates apoptosis via p53- and p38-dependent pathways and is down-regulated in colon cancer. Proc Natl Acad Sci USA 103: 17384-17389
22. Radin NS (2003) Designing anticancer drugs via the achilles heel: ceramide, allylic ketones, and mitochondria. Bioorg Med Chem 11: 2123-2142
23. Ruvolo PP, Deng X, Ito T, Carr BK, May WS (1999) Ceramide induces Bcl2 dephosphorylation via a mechanism involving mitochondrial PP2A. J Biol Chem 274: 20296-20300
24. Samsel L, Zaidel G, Drumgoole HM, Jelovac D, Drachenberg C, Rhee JG, Brodie AM, Bielawska A, Smyth MJ (2004) The ceramide analog, B13, induces apoptosis in prostate cancer cell lines and inhibits tumor growth in prostate cancer xenografts. Prostate 58: 382-393
25. Selzner M, Bielawska A, Morse MA, Rudiger HA, Sindram D, Hannun YA, Clavien PA (2001) Induction of apoptotic cell death and prevention of tumor growth by ceramide analogues in metastatic human colon cancer. Cancer Res 61: 1233-1240
26. Senkal C, Ponnusamy S, Rossi M, Sundararaj K, Szulc Z, Bielawski J, Bielawska A, Meyer M, Cobanoglu B, Koybasi S, Sinha D, Day T, Obeid L, Hannun Y, Ogretmen B (2006) Potent Anti-Tumor 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 317: 1188-1199
27. Szulc ZM, Bielawski J, Gracz H, Gustilo M, Mayroo N, Hannun YA, Obeid LM, Bielawska A (2006) Tailoring structure-function and targeting properties of ceramides by site-specific cationization. Bioorg Med Chem 14: 7083-7104
28. Thon L, Mohlig H, Mathieu S, Lange A, Bulanova E, Winoto-Morbach S, Schutze S, Bulfone-Paus S, Adam D (2005) Ceramide mediates caspase-independent programmed cell death. FASEB J 19: 1945-1956
29. Wattenberg BW, Pitson SM, Raben DM (2006) The sphingosine and diacylglycerol kinase super family of signaling kinases: localization as a key to signaling function. J Lipid Res 47: 1128-1139
30. Yoneda J, Killion JJ, Bucana CD, Fidler IJ (1999) Angiogenesis and growth of murine colon carcinoma are dependent on infiltrating leukocytes. Cancer Biother Radiopharm 14: 221-230