Orlistat Is a Novel Inhibitor of Fatty Acid Synthase with Antitumor Activity

Cancer Research

Volumn 64, Issue 6, 2004, Pages 2070-2075

  Kridel, Steven J ^a   Axelrod, Fumiko ^a   Rozenkrantz, Natasha ^b   Smith, Jeffrey W ^a  

^a BURNHAM INSTITUTE   (United States)

^b ACTIVX BIOSCIENCES INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

TETRAHYDROLIPSTATIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL; CANCER INHIBITION; CELL PROLIFERATION; CONTROLLED STUDY; DRUG ACTIVITY; DRUG APPROVAL; DRUG MECHANISM; DRUG TARGETING; ENZYME INHIBITION; GROWTH INHIBITION; HUMAN; HUMAN CELL; NONHUMAN; NUDE MOUSE; OBESITY; PRIORITY JOURNAL; PROSTATE CANCER; PROTEOMICS; TUMOR CELL;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL DIVISION; ENZYME INHIBITORS; FATTY ACID SYNTHETASE COMPLEX; HUMANS; LACTONES; MALE; MICE; MICE, NUDE; PROSTATIC NEOPLASMS; TUMOR CELLS, CULTURED;

EID: 1542720382     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-03-3645     Document Type: Article

References (31)

1. Ideker T, Galitski T, Hood L. A new approach to decoding life: systems biology. Ann Rev Genomics Hum Genet 2001;2:343-72.
2. Liu Y, Patricelli MP, Cravatt BF. Activity-based protein profiling: the serine hydrolases. Proc Natl Acad Sci USA 1999;96:14694-9.
3. Greenbaum D, Medzihradszky KF, Burlingame A, Bogyo M. Epoxide electrophiles as activity-dependent cysteine protease profiling and discovery tools. Chem Biol 2000;7:569-81.
4. Alo PL, Visca P, Marci A, Mangoni A, Botti C, Di Tondo U. Expression of fatty acid synthase (FAS) as a predictor of recurrence in stage I breast carcinoma patients. Cancer (Phila) 1996;77:474-82.
5. Alo PL, Visca P, Trombetta G, et al. Fatty acid synthase (FAS) predictive strength in poorly differentiated early breast carcinomas. Tumori 1999;85:35-40.
6. Bull JH, Ellison G, Patel A, et al. Identification of potential diagnostic markers of prostate cancer and prostatic intraepithelial neoplasia using cDNA microarray. Br J Cancer 2001;84:1512-9.
7. Furuya Y, Akimoto S, Yasuda K, Ito H. Apoptosis of androgen-independent prostate cell line induced by inhibition of fatty acid synthesis. Anticancer Res 1997;17:4589-93.
8. Gabrielson EW, Pinn ML, Testa JR, Kuhajda FP. Increased fatty acid synthase is a therapeutic target in mesothelioma. Clin Cancer Res 2001;7:153-7.
9. Gansler TS, Hardman W, III, Hunt DA, Schaffel S, Hennigar RA. Increased expression of fatty acid synthase (OA-519) in ovarian neoplasms predicts shorter survival. Hum Pathol 1997;28:686-92.
10. Kidd D, Liu Y, Cravatt B. Profiling serine hydrolase activities in complex proteomes. Biochemistry 2001;40:4005-15.
11. Landry F, Lombardo CR, Smith JW. a method for application of samples to matrix-assisted laser desorption ionization time-of-flight targets that enhances peptide detection. Anal Biochem 2000;279:1-8.
12. Harvey S, Zhang Y, Landry F, Miller C, Smith JW. Insights into a plasma membrane signature. Physiol Genomics 2001;5:129-36.
13. Kuhajda FP, Jenner K, Wood FD, et al. Fatty acid synthesis: a potential selective target for antineoplastic therapy. Proc Natl Acad Sci USA 1994;91:6379-83.
14. Pizer ES, Chrest FJ, DiGiuseppe JA, Han WF. Pharmacological inhibitors of mammalian fatty acid synthase suppress DNA replication and induce apoptosis in tumor cell lines. Cancer Res 1998;58:4611-5.
15. Boven E, Winograd B, Berger DP, et al. Phase II preclinical drug screening in human tumor xenografts: a first European multicenter collaborative study. Cancer Res 1992;52:5940-7.
16. Patricelli MP, Giang DK, Stamp LM, Burbaum JJ. Direct visualizaiton of serine hydrolase activities in complex proteomies using fluorescent active site-directed probes. Proteomics 2001;1:1067-71.
17. Wakil SJ. Fatty acid synthase, a proficient multifunctional enzyme. Biochemistry 1989;28:4523-30.
18. Kuhajda FP. Fatty-acid synthase and human cancer: new perspectives on its role in tumor biology. Nutrition 2000;16:202-8.
19. Moche M, Schneider G, Edwards P, Dehesh K, Lindqvist Y. Structure of the complex between the antibiotic cerulenin and its target, β-ketoacyl-acyl carrier protein synthase. J Biol Chem 1999;274:6031-4.
20. Kuhajda FP, Pizer ES, Li JN, Mani NS, Frehywot GL, Townsend CA. Synthesis and antitumor activity of an inhibitor of fatty acid synthase. Proc Natl Acad Sci USA 2000;97:3450-4.
21. Pizer ES, Wood FD, Heine HS, Romantsev FE, Pasternack GR, Kuhajda FP. Inhibition of fatty acid synthesis delays disease progression in a xenograft model of ovarian cancer. Cancer Res 1996;56:1189-93.
22. Pizer ES, Pflug BR, Bova GS, Han WF, Udan MS, Nelson JB. Increased fatty acid synthase as a therapeutic target in androgen-independent prostate cancer progression. Prostate 2001;47:102-10.
23. Hadvary P, Sidler W, Meister W, Vetter W, Wolfer H. The lipase inhibitor tetrahydrolipstatin binds covalently to the putative active site serine of pancreatic lipase. J Biol Chem 1991;266:2021-7.
24. McNeely W, Benfield P. Orlistat. Drugs 1998;56:241-249.discussion 250.
25. Swinnen JV, Esquenet M, Goossens K, Heyns W, Verhoeven G. Androgens stimulate fatty acid synthase in the human prostate cancer cell line LNCaP. Cancer Res 1997;57:1086-90.
26. Van de Sande T, De Schrijver E, Heyns W, Verhoeven G, Swinnen JV. Role of the phosphatidylinositol 3′-kinase/PTEN/Akt kinase pathway in the overexpression of fatty acid synthase in LNCaP prostate cancer cells. Cancer Res 2002;62:642-6.
27. Kumar-Sinha C, Ignatoski KW, Lippman ME, Ethier SP, Chinnaiyan AM. Transcriptome analysis of HER2 reveals a molecular connection to fatty acid synthesis. Cancer Res 2003;63:132-9.
28. De Schrijver E, Brusselmans K, Heyns W, Verhoeven G, Swinnen JV. RNA interference-mediated silencing of the fatty acid synthase gene attenuates growth and induces morphological changes and apoptosis of LNCaP prostate cancer cells. Cancer Res 2003;63:3799-804.
29. Thupari JN, Landree LE, Ronnett GV, Kuhajda FP. C75 increases peripheral energy utilization and fatty acid oxidation in diet-induced obesity. [comment]. Proc Natl Acad Sci USA 2002;99:9498-502.
30. Romo D, Harrison PH, Jenkins SI, et al. Synthesis and inhibitory action on HMG-CoA synthase of racemic and optically active oxetan-2-ones (β-lactones). Bioorg Med Chem 1998;6:1255-72.
31. Yang HW, Zhao CX, Romo D. Studies of the tandem mukaiyama aldollactonization (TMAL) reaction: a concise and highly diastereoselective route to B-lactones applied to the total synthesis of the potent pancreatic lipase inhibitor, (-)-Panclicin D. Tetrahedron 1997;53:16471-88.