Inhibition of fatty acid synthase in melanoma cells activates the intrinsic pathway of apoptosis

Laboratory Investigation

Volumn 91, Issue 2, 2011, Pages 232-240

  Zecchin, Karina G ^a   Rossato, Franco A ^a   Raposo, Helena F ^a   Melo, Daniela R ^a   Alberici, Luciane C ^b   Oliveira, Helena Cf ^a   Castilho, Roger F ^a   Coletta, Ricardo D ^a   Vercesi, Aníbal E ^a   Graner, Edgard ^a  

^a UNIVERSITY OF CAMPINAS   (Brazil)

^b UNIVERSITY OF SÃO PAULO   (Brazil)

Author keywords

apoptosis; B16 F10 cells; cerulenin; fatty acid synthase; melanoma; orlistat

Indexed keywords

CASPASE 3; CASPASE 9; CERULENIN; CYTOCHROME C; FATTY ACID SYNTHASE INHIBITOR; PROTEIN P53; REACTIVE OXYGEN METABOLITE; TETRAHYDROLIPSTATIN;

ANIMAL CELL; APOPTOSIS; ARTICLE; CELL ACTIVATION; CELL PROLIFERATION; LYMPH NODE METASTASIS; MELANOMA CELL; MITOCHONDRION; NONHUMAN; PRIORITY JOURNAL;

ANALYSIS OF VARIANCE; ANIMALS; APOPTOSIS; CALCIUM; CASPASES; CELL CYCLE; CELL LINE, TUMOR; CELL PROLIFERATION; CELL SURVIVAL; CERULENIN; CYTOCHROMES C; DNA PRIMERS; ENZYME-LINKED IMMUNOSORBENT ASSAY; FATTY ACID SYNTHESIS INHIBITORS; FATTY ACID SYNTHETASE COMPLEX; FLOW CYTOMETRY; LACTONES; LIPIDS; MELANOMA; MICE; REACTIVE OXYGEN SPECIES; RNA INTERFERENCE;

EID: 79551577924     PISSN: 00236837     EISSN: 15300307     Source Type: Journal    
DOI: 10.1038/labinvest.2010.157     Document Type: Article

References (56)

1. Smith S. The animal fatty acid synthase: one gene, one polypeptide, seven enzymes. FASEB J 1994;8:1248-1259.
2. Menendez JA, Lupu R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer 2007;7:763-777.
3. Brink J, Ludtke SJ, Yang CY, et al. Quaternary structure of human fatty acid synthase by electron cryomicroscopy. Proc Natl Acad Sci USA 2002;99:138-143.
4. Weiss L, Hoffmann GE, Schreiber R, et al. Fatty-acid biosynthesis in man, a pathway of minor importance. Purification, optimal assay conditions, and organ distribution of fatty-acid synthase. Biol Chem Hoppe Seyler 1986;367:905-912.
5. Kuhajda FP. Fatty-acid synthase and human cancer: new perspectives on its role in tumor biology. Nutrition 2000;16:202-208.
6. Alo PL, Visca P, Framarino ML, et al. Immunohistochemical study of fatty acid synthase in ovarian neoplasms. Oncol Rep 2000;7: 1383-1388.
7. Pizer ES, Jackisch C, Wood FD, et al. Inhibition of fatty acid synthesis induces programmed cell death in human breast cancer cells. Cancer Res 1996;56:2745-2747.
8. Pizer ES, Wood FD, Heine HS, et al. Inhibition of fatty acid synthesis delays disease progression in a xenograft model of ovarian cancer. Cancer Res 1996;56:1189-1193.
9. Gansler TS, Hardman III W, Hunt DA, et al. Increased expression of fatty acid synthase (OA-519) in ovarian neoplasms predicts shorter survival. Hum Pathol 1997;28:686-692.
10. Dhanasekaran SM, Barrette TR, Ghosh D, et al. Delineation of prognostic biomarkers in prostate cancer. Nature 2001;412:822-826.
11. Swinnen JV, Roskams T, Joniau S, et al. Overexpression of fatty acid synthase is an early and common event in the development of prostate cancer. Int J Cancer 2002;98:19-22.
12. Innocenzi D, Alo PL, Balzani A, et al. Fatty acid synthase expression in melanoma. J Cutan Pathol 2003;30:23-28.
13. Rossi S, Graner E, Febbo P, et al. Fatty acid synthase expression defines distinct molecular signatures in prostate cancer. Mol Cancer Res 2003;1:707-715.
14. Takahiro T, Shinichi K, Toshimitsu S. Expression of fatty acid synthase as a prognostic indicator in soft tissue sarcomas. Clin Cancer Res 2003;9:2204-2212.
15. Visca P, Sebastiani V, Botti C, et al. Fatty acid synthase (FAS) is a marker of increased risk of recurrence in lung carcinoma. Anticancer Res 2004;24:4169-4173.
16. Kapur P, Rakheja D, Roy LC, et al. Fatty acid synthase expression in cutaneous melanocytic neoplasms. Mod Pathol 2005;18:1107-1112.
17. van de Sande T, Roskams T, Lerut E, et al. High-level expression of fatty acid synthase in human prostate cancer tissues is linked to activation and nuclear localization of Akt/PKB. J Pathol 2005;206:214-219.
18. Rossi S, Ou W, Tang D, et al. Gastrointestinal stromal tumours overexpress fatty acid synthase. J Pathol 2006;209:369-375.
19. Dowling S, Cox J, Cenedella RJ. Inhibition of fatty acid synthase by Orlistat accelerates gastric tumor cell apoptosis in culture and increases survival rates in gastric tumor bearing mice in vivo. Lipids 2009;44:489-498.
20. Furuya Y, Akimoto S, Yasuda K, et al. Apoptosis of androgenindependent prostate cell line induced by inhibition of fatty acid synthesis. Anticancer Res 1997;17:4589-4593.
21. Pizer ES, Chrest FJ, DiGiuseppe JA, et al. Pharmacological inhibitors of mammalian fatty acid synthase suppress DNA replication and induce apoptosis in tumor cell lines. Cancer Res 1998;58:4611-4615.
22. Li JN, Gorospe M, Chrest FJ, et al. Pharmacological inhibition of fatty acid synthase activity produces both cytostatic and cytotoxic effects modulated by p53. Cancer Res 2001;61:1493-1499.
23. Zhou W, Han WF, Landree LE, et al. Fatty acid synthase inhibition activates AMP-activated protein kinase in SKOV3 human ovarian cancer cells. Cancer Res 2007;67:2964-2971.
24. Kridel SJ, Axelrod F, Rozenkrantz N, et al. Orlistat is a novel inhibitor of fatty acid synthase with antitumor activity. Cancer Res 2004;64: 2070-2075.
25. Alli PM, Pinn ML, Jaffee EM, et al. Fatty acid synthase inhibitors are chemopreventive for mammary cancer in neu-N transgenic mice. Oncogene 2005;24:39-46.
26. Bandyopadhyay S, Zhan R, Wang Y, et al. Mechanism of apoptosis induced by the inhibition of fatty acid synthase in breast cancer cells. Cancer Res 2006;66:5934-5940.
27. Heiligtag SJ, Bredehorst R, David KA. Key role of mitochondria in cerulenin-mediated apoptosis. Cell Death Differ 2002;9:1017-1025.
28. Liu X, Shi Y, Giranda VL, et al. Inhibition of the phosphatidylinositol 3-kinase/Akt pathway sensitizes MDA-MB468 human breast cancer cells to cerulenin-induced apoptosis. Mol Cancer Ther 2006;5:494-501.
29. Carvalho M.A., Zecchin KG, Seguin F, et al. Fatty acid synthase inhibition with Orlistat promotes apoptosis and reduces cell growth and lymph node metastasis in a mouse melanoma model. Int J Cancer 2008;123:2557-2565.
30. Knowles LM, Axelrod F, Browne CD, et al. A fatty acid synthase blockade induces tumor cell-cycle arrest by down-regulating Skp2. J Biol Chem 2004;279:30540-30545.
31. Chen Y, McMillan-Ward E, Kong J, et al. Oxidative stress induces autophagic cell death independent of apoptosis in transformed and cancer cells. Cell Death Differ 2008;15:171-182.
32. LeBel CP, Ischiropoulos H, Bondy SC. Evaluation of the probe 20 , 70-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 1992;5:227-231.
33. Payne CM, Weber C, Crowley-Skillicorn C, et al. Deoxycholate induces mitochondrial oxidative stress and activates NF-kappaB through multiple mechanisms in HCT-116 colon epithelial cells. Carcinogenesis 2007;28:215-222.
34. Zecchin KG, Seidinger AL, Chiaratti MR, et al. High Bcl-2/Bax ratio in Walker tumor cells protects mitochondria but does not prevent H2O2- induced apoptosis via calcineurin pathways. J Bioenerg Biomembr 2007;39:186-194.
35. Tsien RY. Fluorescence measurement and photochemical manipulation of cytosolic free calcium. Trends Neurosci 1988;11:419-424.
36. Abou-Khalil S, Abou-Khalil WH, Planas L, et al. Interaction of rhodamine 123 with mitochondria isolated from drug-sensitive and -resistant Friend leukemia cells. Biochem Biophys Res Commun 1985;127: 1039-1044.
37. Shepherd D, Garland PB. ATP controlled acetoacetate and citrate synthesis by rat liver mitochondria oxidising palmitoyl-carnitine, and the inhibition of citrate synthase by ATP. Biochem Biophys Res Commun 1966;22:89-93.
38. Campos CB, Paim BA, Cosso RG, et al. Method for monitoring of mitochondrial cytochrome c release during cell death: Immunodetection of cytochrome c by flow cytometry after selective permeabilization of the plasma membrane. Cytometry Part A 2006;69: 515-523.
39. Green DR, Reed JC. Mitochondria and apoptosis. Science 1998; 281:1309-1312.
40. Garrido C, Galluzzi L, Brunet M, et al. Mechanisms of cytochrome c release from mitochondria. Cell Death Differ 2006;13:1423-1433.
41. Ho TS, Ho YP, Wong WY, et al. Fatty acid synthase inhibitors cerulenin and C75 retard growth and induce caspase-dependent apoptosis in human melanoma A-375 cells. Biomed Pharmacother 2007;61: 578-587.
42. Menendez JA, Vellon L, Lupu R. Antitumoral actions of the anti-obesity drug orlistat (XenicalTM) in breast cancer cells: blockade of cell cycle progression, promotion of apoptotic cell death and PEA3-mediated transcriptional repression of Her2/neu (erbB-2) oncogene. Ann Oncol 2005;16:1253-1267.
43. Menendez JA, Vellon L, Lupu R. Orlistat: from antiobesity drug to anticancer agent in Her-2/neu (erbB-2)-overexpressing gastrointestinal tumors? Exp Biol Med (Maywood) 2005;230:151-154.
44. Kroemer G, Galluzzi L, Vandenabeele P, et al. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ 2009;16:3-11.
45. Straub SG, Sharp GWG. Inhibition of insulin secretion by cerulenin might be due to impaired glucose metabolism. Diabetes Metab Res Rev 2007;23:146-151.
46. Chajes V, Cambot M, Moreau K, et al. Acetyl-CoA carboxylase alpha is essential to breast cancer cell survival. Cancer Res 2006;66:5287-5294.
47. Migita T, Ruiz S, Fornari A, et al. Fatty acid synthase: a metabolic enzyme and candidate oncogene in prostate cancer. J Natl Cancer Inst 2009;101:519-532.
48. Lotem J, Kama R, Sachs L. Suppression or induction of apoptosis by opposing pathways downstream from calcium-activated calcineurin. Proc Natl Acad Sci USA 1999;96:12016-12020.
49. Wang HG, Pathan N, Ethell IM, et al. Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD. Science 1999;284: 339-343.
50. Kowaltowski AJ, Castilho RF, Vercesi AE. Mitochondrial permeability transition and oxidative stress. FEBS Lett 2001;495:12-15.
51. Pizer ES, Thupari J, Han WF, et al. Malonyl-coenzyme-A is a potential mediator of cytotoxicity induced by fatty-acid synthase inhibition in human breast cancer cells and xenografts. Cancer Res 2000;60: 213-218.
52. Thupari JN, Pinn ML, Kuhajda FP. Fatty acid synthase inhibition in human breast cancer cells leads to malonyl-CoA-induced inhibition of fatty acid oxidation and cytotoxicity. Biochem Biophys Res Commun 2001;285:217-223.
53. Zhang Y, Guo C, Yu G. A pilot study of fatty acid metabolism in oral squamous cell carcinoma. Int J Oral Maxillofac Surg 2005;34:78-81.
54. Paumen MB, Ishida Y, Han H, et al. Direct interaction of the mitochondrial membrane protein carnitine palmitoyltransferase I with Bcl-2. Biochem Biophys Res Commun 1997;231:523-525.
55. Uddin S, Siraj AK, Al-Rasheed M, et al. Fatty acid synthase and AKT pathway signaling in a subset of papillary thyroid cancers. J Clin Endocrinol Metab 2008;93:4088-4097.
56. Mo H, Elson CE. Apoptosis and cell-cycle arrest in human and murine tumor cells are initiated by isoprenoids. J Nutr 1999;129:804-813