{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T04:19:15Z","timestamp":1791778755461,"version":"4.3.4"},"reference-count":58,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2008,9,3]],"date-time":"2008-09-03T00:00:00Z","timestamp":1220400000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fatty acid synthase (FASN) is the enzyme responsible for the endogenous synthesis of the saturated fatty acid palmitate. In contrast to most normal cells, malignant cells depend on FASN activity for growth and survival. In fact, FASN is overexpressed in a variety of human cancers including cutaneous melanoma, in which its levels of expression are associated with a poor prognosis and depth of invasion. Here, we show that the specific inhibition of FASN activity by the antiobesity drug Orlistat or siRNA is able to significantly reduce proliferation and promote apoptosis in the mouse metastatic melanoma cell line B16\u2010F10. These results prompted us to verify the effect of FASN inhibition on the metastatic process in a model of spontaneous melanoma metastasis, in which B16\u2010F10 cells injected in the peritoneal cavity of C57BL\/6 mice metastasize to the mediastinal lymph nodes. We observed that mice treated with Orlistat 48 hr after the inoculation of B16\u2010F10 cells exhibited a 52% reduction in the number of mediastinal lymph node metastases, in comparison with the control animals. These results suggest that FASN activity is essential for B16\u2010F10 melanoma cell proliferation and survival while its inactivation by Orlistat significantly reduces their metastatic spread. The chemical inhibition of FASN activity could have a potential benefit in association with the current chemotherapy for melanoma. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.23835","type":"journal-article","created":{"date-parts":[[2008,9,3]],"date-time":"2008-09-03T18:08:46Z","timestamp":1220465326000},"page":"2557-2565","source":"Crossref","is-referenced-by-count":145,"title":["Fatty acid synthase inhibition with Orlistat promotes apoptosis and reduces cell growth and lymph node metastasis in a mouse melanoma model"],"prefix":"10.1002","volume":"123","author":[{"given":"Marco A.","family":"Carvalho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina G.","family":"Zecchin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Seguin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9bora C.","family":"Bastos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Agostini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana L\u00facia C.A.","family":"Rangel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00edlvio S.","family":"Veiga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena F.","family":"Raposo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena C.F.","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Loda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo D.","family":"Coletta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgard","family":"Graner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,9,3]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0899-9007(99)00266-X"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1515\/bchm3.1986.367.2.905"},{"key":"e_1_2_6_4_2","first-page":"1189","article-title":"Inhibition of fatty acid synthesis delays disease progression in a xenograft model of ovarian cancer","volume":"56","author":"Pizer ES","year":"1996","journal-title":"Cancer Res"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(97)90177-5"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19960201)77:3<474::AID-CNCR8>3.0.CO;2-K"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0347(199907)21:4<325::AID-HED6>3.0.CO;2-P"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1053\/hupa.2000.9842"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/35090585"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(96)90218-X"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2559.2002.01289.x"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.10127"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0560.2003.300104.x"},{"key":"e_1_2_6_14_2","first-page":"707","article-title":"Fatty acid synthase expression defines distinct molecular signatures in prostate cancer","volume":"1","author":"Rossi S","year":"2003","journal-title":"Mol Cancer Res"},{"key":"e_1_2_6_15_2","first-page":"335","article-title":"Immunohistochemical expression and prognostic significance of FAS and GLUT1 in bladder carcinoma","volume":"23","author":"Visca P","year":"2003","journal-title":"Anticancer Res"},{"key":"e_1_2_6_16_2","first-page":"2204","article-title":"Expression of fatty acid synthase as a prognostic indicator in soft tissue sarcomas","volume":"9","author":"Takahiro T","year":"2003","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1983"},{"key":"e_1_2_6_18_2","first-page":"4589","article-title":"Apoptosis of androgen\u2010independent prostate cell line induced by inhibition of fatty acid synthesis","volume":"17","author":"Furuya Y","year":"1997","journal-title":"Anticancer Res"},{"key":"e_1_2_6_19_2","first-page":"4611","article-title":"Pharmacological inhibitors of mammalian fatty acid synthase suppress DNA replication and induce apoptosis in tumor cell lines","volume":"58","author":"Pizer ES","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_6_20_2","first-page":"1493","article-title":"Pharmacological inhibition of fatty acid synthase activity produces both cytostatic and cytotoxic effects modulated by p53","volume":"61","author":"Li JN","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_6_21_2","first-page":"7330","article-title":"Fatty acid synthase inhibition triggers apoptosis during S phase in human cancer cells","volume":"63","author":"Zhou W","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.1052"},{"key":"e_1_2_6_23_2","first-page":"213","article-title":"Malonyl\u2010coenzyme\u2010A is a potential mediator of cytotoxicity induced by fatty\u2010acid synthase inhibition in human breast cancer cells and xenografts","volume":"60","author":"Pizer ES","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208174"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-3645"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1177\/153537020523000301"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdi239"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405061200"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008556200"},{"key":"e_1_2_6_30_2","first-page":"1086","article-title":"Androgens stimulate fatty acid synthase in the human prostate cancer cell line LNCaP","volume":"57","author":"Swinnen JV","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203889"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend.15.10.0703"},{"key":"e_1_2_6_33_2","first-page":"642","article-title":"Role of the phosphatidylinositol 3\u2032\u2010kinase\/PTEN\/Akt kinase pathway in the overexpression of fatty acid synthase in LNCaP prostate cancer cells","volume":"62","author":"Van de Sande T","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(04)00055-8"},{"key":"e_1_2_6_35_2","volume-title":"SEER Cancer statistics review, 1975\u20132000","author":"Ries LAG","year":"2003"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3800395"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910390324"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)33493-3"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgh261"},{"key":"e_1_2_6_41_2","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1016\/S0022-2275(20)34420-5","article-title":"Measurement of rates of cholesterol synthesis using tritiated water","volume":"25","author":"Dietschy JM","year":"1984","journal-title":"J Lipid Res"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117760"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-2095fje"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)41878-4"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.137.10.4468"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M313701200"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199856020-00007"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2007.08.020"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0931394100"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1983"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1060"},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)00265-1"},{"key":"e_1_2_6_53_2","first-page":"1636","article-title":"In vitro selection of murine B16 melanoma variants with enhanced tissue\u2010invasive properties","volume":"40","author":"Poste G","year":"1980","journal-title":"Cancer Res"},{"key":"e_1_2_6_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/newbio242148a0"},{"key":"e_1_2_6_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01782483"},{"key":"e_1_2_6_56_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-1757"},{"key":"e_1_2_6_57_2","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.4049\/jimmunol.163.5.2809","article-title":"Mice with a targeted mutation in lymphotoxin\u2010alpha exhibit enhanced tumor growth and metastasis: impaired NK cell development and recruitment","volume":"163","author":"Ito D","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_6_58_2","first-page":"4763","article-title":"Estrous cycle influences organ\u2010specific metastasis of B16F10 melanoma cells","volume":"63","author":"Vantyghem SA","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_6_59_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-5404com"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.23835","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.23835","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T15:38:27Z","timestamp":1697470707000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.23835"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,9,3]]},"references-count":58,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2008,12]]}},"alternative-id":["10.1002\/ijc.23835"],"URL":"https:\/\/doi.org\/10.1002\/ijc.23835","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,9,3]]}}}