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Review

Fatty acid synthase inhibitors: new directions for oncology

, PhD, &
Pages 1817-1829 | Published online: 30 Oct 2007

Bibliography

  • WARBURG O: On the origin of cancer cells. Science (1956) 123:309-314.
  • HOCHACHKA PW, RUPERT JL, GOLDENBERG L, GLEAVE M, KOZLOWSKI P: Going malignant: the hypoxia-cancer connection in the prostate. Bioessays (2002) 24:749-757.
  • PAN JG, MAK TW: Metabolic targeting as an anticancer strategy: dawn of a new era? Sci. STKE (2007):PE12-PE14.
  • 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.
  • WAKIL SJ: Fatty acid synthase, a proficient multifunctional enzyme. Biochemistry (1989) 28:4523-4530.
  • KUHAJDA FP: Fatty acid synthase and cancer: new application of an old pathway. Cancer Res. (2006) 66:5977-5980.
  • KUHAJDA FP: Fatty-acid synthase and human cancer: new perspectives on its role in tumor biology. Nutrition (2000) 16:202-208.
  • SWINNEN JV, BRUSSELMANS K, VERHOEVEN G: Increased lipogenesis in cancer cells: new players, novel targets. Curr. Opin. Clin. Nutr. Metab. Care (2006) 9:358-365.
  • OOKHTENS M, KANNAN R, LYON I, BAKER N: Liver and adipose tissue contributions to newly formed fatty acids in an ascites tumor. Am. J. Physiol. Regul. Integr. Comp. Physiol. (1984) 247:R146-R153.
  • EPSTEIN JI, CARMICHAEL M, PARTIN AW: OA-519 (fatty acid synthase) as an independent predictor of pathologic state in adenocarcinoma of the prostate. Urology (1995) 45:81-86.
  • 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) 47:102-110.
  • 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.
  • SHURBAJI MS, KALBFLEISCH JH, THURMOND TS: Immunohistochemical detection of a fatty acid synthase (OA-519) as a predictor of progression of prostate cancer. Hum. Pathol. (1996) 27:917-921.
  • 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 (1996) 77:474-482.
  • MILGRAUM LZ, WITTERS LA, PASTERNACK GR, KUHAJDA FP: Enzymes of the fatty acid synthesis pathway are highly expressed in in situ breast carcinoma. Clin. Cancer Res. (1997) 3:2115-2120.
  • NAKAMURA I, KIMIJIMA I, ZHANG GJ et al.: Fatty acid synthase expression in Japanese breast carcinoma patients. Int. J. Mol. Med. (1999) 4:381-387.
  • 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.
  • RASHID A, PIZER ES, MOGA M et al.: Elevated expression of fatty acid synthase and fatty acid synthetic activity in colorectal neoplasia. Am. J. Pathol. (1997) 150:201-208.
  • 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) 28:686-692.
  • ALO PL, VISCA P, FRAMARINO ML et al.: Immunohistochemical study of fatty acid synthase in ovarian neoplasms. Oncol. Rep. (2000) 7:1383-1388.
  • SEBASTIANI V, VISCA P, BOTTI C et al.: Fatty acid synthase is a marker of increased risk of recurrence in endometrial carcinoma. Gynecol. Oncol. (2004) 92:101-105.
  • VISCA P, SEBASTIANI V, PIZER ES et al.: Immunohistochemical expression and prognostic significance of FAS and GLUT1 in bladder carcinoma. Anticancer Res. (2003) 23:335-339.
  • 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.
  • PIYATHILAKE CJ, FROST AR, MANNE U et al.: The expression of fatty acid synthase (FASE) is an early event in the development and progression of squamous cell carcinoma of the lung. Hum. Pathol. (2000) 31:1068-1073.
  • INNOCENZI D, ALO PL, BALZANI A et al.: Fatty acid synthase expression in melanoma. J. Cutaneous Pathol. (2003) 30:23-28.
  • CAMASSEI FD, COZZA R, ACQUAVIVA A et al.: Expression of the lipogenic enzyme fatty acid synthase (FAS) in retinoblastoma and its correlation with tumor aggressiveness. Invest. Ophthalmol. Vis. Sci. (2003) 44:2399-2403.
  • 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.
  • CAMASSEI FD, JENKNER A, RAVA L et al.: Expression of the lipogenic enzyme fatty acid synthase (FAS) as a predictor of poor outcome in nephroblastoma: an interinstitutional study. Med. Pediatr. Oncol. (2003) 40:302-308.
  • KAPUR P, RAKHEJA D, ROY LC, HOANG MP: Fatty acid synthase expression in cutaneous melanocytic neoplasms. Mod. Pathol. (2005) 18:1107-1112.
  • GRANER E, TANG D, ROSSI S et al.: The isopeptidase USP2a regulates the stability of fatty acid synthase in prostate cancer. Cancer Cell (2004) 5:253-261.
  • SHAH US, DHIR R, GOLLIN SM et al.: Fatty acid synthase gene overexpression and copy number gain in prostate adenocarcinoma. Hum. Pathol. (2006) 37:401-409.
  • WANG YY, KUHAJDA FP, JINONG L et al.: Fatty acid synthase as a tumor marker: its extracellular expression in human breast cancer. J. Exp. Ther. Oncol. (2004) 4:101-110.
  • WANG Y, KUHAJDA FP, LI JN et al.: Fatty acid synthase (FAS) expression in human breast cancer cell culture supernatants and in breast cancer patients. Cancer Lett. (2001) 167:99-104.
  • CHIRALA SS, CHANG H, MATZUK M et al.: Fatty acid synthesis is essential in embryonic development: fatty acid synthase null mutants and most of the heterozygotes die in utero. Proc. Natl. Acad. Sci. USA (2003) 100:6358-6363.
  • ABU-ELHEIGA L, MATZUK MM, KORDARI P et al.: Mutant mice lacking acetyl-CoA carboxylase 1 are embryonically lethal. Proc. Natl. Acad. Sci. USA (2005) 102:12011-12016.
  • MAO J, DEMAYO FJ, LI H et al.: Liver-specific deletion of acetyl-CoA carboxylase 1 reduces hepatic triglyceride accumulation without affecting glucose homeostasis. Proc. Natl. Acad. Sci. USA (2006) 103:8552-8557.
  • CHAKRAVARTHY MV, PAN Z, ZHU Y et al.: ‘New’ hepatic fat activates PPAR[α] to maintain glucose, lipid, and cholesterol homeostasis. Cell Metab. (2005) 1:309-322.
  • SWINNEN JV, VAN VELDHOVEN PP, TIMMERMANS L et al.: Fatty acid synthase drives the synthesis of phospholipids partitioning into detergent-resistant membrane microdomains. Biochem. Biophys. Res. Commun. (2003) 302:898-903.
  • RESH MD: Trafficking and signaling by fatty-acylated and prenylated proteins. Nat. Chem. Biol. (2006) 2:584-590.
  • RESH MD: Use of analogs and inhibitors to study the functional significance of protein palmitoylation. Methods (2006) 40:191-197.
  • BARON A, MIGITA T, TANG D, LODA M: Fatty acid synthase: a metabolic oncogene in prostate cancer? J. Cell Biochem. (2004) 91:47-53.
  • FUNABASHI H, KAWAGUCHI A, TOMODA H, OMURA S, OKUDA S, IWASAKI S: Binding site of cerulenin in fatty acid synthetase. J. Biochem. (Tokyo) (1989) 105:751-755.
  • PIZER ES, JACKISCH C, WOOD FD, PASTERNACK GR, DAVIDSON NE, KUHAJDA FP: Inhibition of fatty acid synthesis induces programmed cell death in human breast cancer cells. Cancer Res. (1996) 56:2745-2747.
  • 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) 56:1189-1193.
  • 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) 63:3799-3804.
  • 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.
  • 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) 58:4611-4615.
  • 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.
  • HEILIGTAG SJ, BREDEHORST R, DAVID KA: Key role of mitochondria in cerulenin-mediated apoptosis. Cell Death Differ. (2002) 9:1017-1025.
  • 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) 97:3450-3454.
  • 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.
  • GABRIELSON EW, PINN ML, TESTA JR, KUHAJDA FP: Increased fatty acid synthase is a therapeutic target in mesothelioma. Clin. Cancer Res. (2001) 7:153-157.
  • WANG HQ, ALTOMARE DA, SKELE KL et al.: Positive feedback regulation between AKT activation and fatty acid synthase expression in ovarian carcinoma cells. Oncogene (2005) 24:3574-3582.
  • 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.
  • MENENDEZ JA, VELLON L, MEHMI I et al.: Inhibition of fatty acid synthase (FAS) suppresses HER2/neu (erbB-2) oncogene overexpression in cancer cells. Proc. Natl. Acad. Sci. USA (2004) 101:10715-10720.
  • LIU X, SHI Y, GIRANDA VL, LUO Y: 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.
  • 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.
  • BANDYOPADHYAY S, PAI SK, WATABE M et al.: FAS expression inversely correlates with PTEN level in prostate cancer and a PI3-kinase inhibitor synergizes with FAS siRNA to induce apoptosis. Oncogene (2005) 24:5389-5395.
  • FREEMAN MR, CINAR B, LU ML: Membrane rafts as potential sites of nongenomic hormonal signaling in prostate cancer. Trends Endocrinol. Metab. (2005) 16:273-279.
  • ALLI PM, PINN ML, JAFFEE EM, MCFADDEN JM, KUHAJDA FP: Fatty acid synthase inhibitors are chemopreventive for mammary cancer in neu-N transgenic mice. Oncogene (2005) 24:39-46.
  • MCFADDEN JM, MEDGHALCHI SM, THUPARI JN et al.: Application of a flexible synthesis of (5R)-thiolactomycin to develop new inhibitors of type I fatty acid synthase. J. Med. Chem. (2005) 48:946-961.
  • MCFADDEN JM, FREHYWOT GL, TOWNSEND CA: A flexible route to (5R)-thiolactomycin, a naturally occurring inhibitor of fatty acid synthesis. Org. Lett. (2002) 4:3859-3862.
  • KRIDEL SJ, AXELROD F, ROZENKRANTZ N, SMITH JW: Orlistat is a novel inhibitor of fatty acid synthase with antitumor activity. Cancer Res. (2004) 64:2070-2075.
  • KNOWLES LM, AXELROD F, BROWNE CD, SMITH JW: A fatty acid synthase blockade induces tumor cell-cycle arrest by down-regulating Skp2. J. Biol. Chem. (2004) 279:30540-30545.
  • PIZER ES, CHREST FJ, DI GIUSEPPE JA, HAN WF: Pharmacological inhibitors of mammalian fatty acid synthase suppress DNA replication and induce apoptosis in tumor cell lines. Cancer Res. (1998) 58:4611-4615.
  • ZHOU W, SIMPSON PJ, MCFADDEN JM et al.: Fatty acid synthase inhibition triggers apoptosis during s phase in human cancer cells. Cancer Res. (2003) 63:7330-7337.
  • MA G, ZANCANELLA M, OYOLA Y, RICHARDSON RD, SMITH JW, ROMO D: Total synthesis and comparative analysis of orlistat, valilactone, and a transposed orlistat derivative: inhibitors of fatty acid synthase. Org. Lett. (2006) 8:4497-4500.
  • PUROHIT VC, RICHARDSON RD, SMITH JW, ROMO D: Practical, catalytic, asymmetric synthesis of β-lactones via a sequential ketene dimerization/hydrogenation process: inhibitors of the thioesterase domain of fatty acid synthase. J. Org. Chem. (2006) 71:4549-4558.
  • TIAN WX: Inhibition of fatty acid synthase by polyphenols. Curr. Med. Chem. (2006) 13:967-977.
  • WANG X, TIAN W: Green tea epigallocatechin gallate: a natural inhibitor of fatty-acid synthase. Biochem. Biophys. Res. Commun. (2001) 288:1200-1206.
  • LI BH, MA XF, WANG Y, TIAN WX: Structure–activity relationship of polyphenols that inhibit fatty acid synthase. J. Biochem. (Tokyo) (2005) 138:679-685.
  • BRUSSELMANS K, DE SCHRIJVER E, HEYNS W, VERHOEVEN G, SWINNEN JV: Epigallocatechin-3-gallate is a potent natural inhibitor of fatty acid synthase in intact cells and selectively induces apoptosis in prostate cancer cells. Int. J. Cancer (2003) 106:856-862.
  • LIAO S, UMEKITA Y, GUO J, KOKONTIS JM, HIIPAKKA RA: Growth inhibition and regression of human prostate and breast tumors in athymic mice by tea epigallocatechin gallate. Cancer Lett. (1995) 96:239-243.
  • THANGAPAZHAM RL, SINGH AK, SHARMA A, WARREN J, GADDIPATI JP, MAHESHWARI RK: Green tea polyphenols and its constituent epigallocatechin gallate inhibits proliferation of human breast cancer cells in vitro and in vivo. Cancer Lett. (2007) 245:232-241.
  • SPINELLA F, ROSANO L, DI CASTRO V et al.: Green tea polyphenol epigallocatechin-3-gallate inhibits the endothelin axis and downstream signaling pathways in ovarian carcinoma. Mol. Cancer Ther. (2006) 5:1483-1492.
  • KHAN N, AFAQ F, SALEEM M, AHMAD N, MUKHTAR H: Targeting multiple signaling pathways by green tea polyphenol (-)-epigallocatechin-3-gallate. Cancer Res. (2006) 66:2500-2505.
  • BRUSSELMANS K, VROLIX R, VERHOEVEN G, SWINNEN JV: Induction of cancer cell apoptosis by flavonoids is associated with their ability to inhibit fatty acid synthase activity. J. Biol. Chem. (2005) 280:5636-5645.
  • LI BH, TIAN WX: Inhibitory effects of flavonoids on animal fatty acid synthase. J. Biochem. (Tokyo) (2004) 135:85-91.
  • 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.
  • BRUSSELMANS K, DE SCHRIJVER E, VERHOEVEN G, SWINNEN JV: RNA interference-mediated silencing of the acetyl-CoA-carboxylase-α gene induces growth inhibition and apoptosis of prostate cancer cells. Cancer Res. (2005) 65:6719-6725.
  • CHAJES V, CAMBOT M, MOREAU K, LENOIR GM, JOULIN V: Acetyl-CoA carboxylase {α} is essential to breast cancer cell survival. Cancer Res. (2006) 66:5287-5294.
  • LITTLE JL, WHEELER FB, FELS DR, KOUMENIS C, KRIDEL SJ: Inhibition of fatty acid synthase induces endoplasmic reticulum stress in tumor cells. Cancer Res. (2007) 67:1262-1269.
  • 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.
  • HATZIVASSILIOU G, ZHAO F, BAUER DE et al.: ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell (2005) 8:311-321.
  • BAUER DE, HATZIVASSILIOU G, ZHAO F, ANDREADIS C, THOMPSON CB: ATP citrate lyase is an important component of cell growth and transformation. Oncogene (2005) 24:6314-6322.
  • XIANG X, SAHA AK, WEN R, RUDERMAN NB, LUO Z: AMP-activated protein kinase activators can inhibit the growth of prostate cancer cells by multiple mechanisms. Biochem. Biophys. Res. Commun. (2004) 321:161-167.
  • RATTAN R, GIRI S, SINGH AK, SINGH I: 5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside inhibits cancer cell proliferation in vitro and in vivo via AMP-activated protein kinase. J. Biol. Chem. (2005) 280:39582-39593.
  • BECKERS A, ORGANE S, TIMMERMANS L et al.: Methotrexate enhances the antianabolic and antiproliferative effects of 5-aminoimidazole-4-carboxamide riboside. Mol. Cancer Ther. (2006) 5:2211-2217.
  • CHIRALA SS, WAKIL SJ: Structure and function of animal fatty acid synthase. Lipids (2004) 39:1045-1053.
  • SMITH S, WITKOWSKI A, JOSHI AK: Structural and functional organization of the animal fatty acid synthase. Prog. Lipid Res. (2003) 42:289-317.
  • ASTURIAS FJ, CHADICK JZ, CHEUNG IK et al.: Structure and molecular organization of mammalian fatty acid synthase. Nat. Struct. Mol. Biol. (2005) 12:225-232.
  • BRINK J, LUDTKE SJ, KONG Y, WAKIL SJ, MA J, CHIU W: Experimental verification of conformational variation of human fatty acid synthase as predicted by normal mode analysis. Structure (Camb.) (2004) 12:185-191.
  • MAIER T, JENNI S, BAN N: Architecture of mammalian fatty acid synthase at 4.5 Å resolution. Science (2006) 311:1258-1262.
  • PRICE AC, CHOI KH, HEATH RJ, LI Z, WHITE SW, ROCK CO: Inhibition of β-ketoacyl–acyl carrier protein synthases by thiolactomycin and cerulenin. Structure and mechanism. J. Biol. Chem. (2001) 276:6551-6559.
  • 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) 274:6031-6034.
  • 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) 97:3450-3454.
  • PEMBLE CW, JOHNSON LC, KRIDEL SJ, LOWTHER WT: Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by orlistat. Nat. Struct. Mol. Biol. (2007) 14:704-709.
  • CHAKRAVARTY B, GU Z, CHIRALA SS, WAKIL SJ, QUIOCHO FA: Human fatty acid synthase: structure and substrate selectivity of the thioesterase domain. Proc. Natl. Acad. Sci. USA (2004) 101:15567-15572.
  • SCHODER H, LARSON SM: Positron emission tomography for prostate, bladder, and renal cancer. Semin. Nucl. Med. (2004) 34:274-292.
  • DIMITRAKOPOULOU-STRAUSS A, STRAUSS LG: PET imaging of prostate cancer with 11C-acetate. J. Nucl. Med. (2003) 44:556-558.
  • LEE J, ORITA H, GABRIELSON K et al.: FDG-PET for pharmacodynamic assessment of the fatty acid synthase inhibitor C75 in an experimental model of lung cancer. Pharm. Res. (2007) 24:1202-1207.

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