{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T20:45:10Z","timestamp":1771188310772,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2002,8,1]],"date-time":"2002-08-01T00:00:00Z","timestamp":1028160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Lipids"],"published-print":{"date-parts":[[2002,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Eicosapentaenoic acid (EPA; 20\u22365n\u22123) may reduce the cell number in cultured leukemia\/lymphoma cells owing to reduced cell proliferation, induction of cell death, or a combination of these processes. EPA has been shown to promote apoptosis in Ramos cells, and our present study was focused on a possible cell cycle arrest and the pathways by which the apoptotic process is induced. Apoptosis may proceed along the intrinsic (mitochondrial) or the extrinsic (death receptor) pathway, which are mediated <jats:italic>via<\/jats:italic> different caspases. Caspases are a class of homologous cysteine proteases recognized as pivotal mediators of apoptosis. We investigated whether EPA affects progression of the cell cycle or promotes apoptosis directly. By incorporation of [<jats:sup>3<\/jats:sup>H]thymidine and [<jats:sup>3<\/jats:sup>H]valine, we showed that DNA, as well as protein synthesis, was reduced after incubation of Ramos cells with EPA for 6h. We monitored cell cycle distribution by 5\u2010bromo\u20102\u2032\u2010deoxyuridine staining and observed no cell cycle arrest in the EPA\u2010incubated cells. Incubation of cells with EPA caused PS\u2010flipping, as demonstrated by annexin V\u2010binding (flow cytometry), and cleavage of poly(ADP\u2010ribose) polymerase measured by Western blot analysis. Furthermore, we observed increased activity of caspase\u20103 and\u20109, but not of caspase\u20108. Whereas inhibitors of caspase\u20103 and\u20109 reduced EPA\u2010induced apoptosis, inhibition of caspase\u20108 did not. This suggests that EPA may promote apoptosis <jats:italic>via<\/jats:italic> the intrinsic pathway in Ramos cells. Thus, the reduction in cell number can be explained by a direct apoptotic effect of EPA rather than <jats:italic>via<\/jats:italic> cell cycle arrest.<\/jats:p>","DOI":"10.1007\/s11745-002-0963-6","type":"journal-article","created":{"date-parts":[[2006,11,13]],"date-time":"2006-11-13T19:16:19Z","timestamp":1163445379000},"source":"Crossref","is-referenced-by-count":33,"title":["Eicosapentaenoic acid promotes apoptosis in Ramos cells <i>via<\/i> activation of caspase\u20103 and \u20109"],"prefix":"10.1002","volume":"37","author":[{"given":"Hilde","family":"Heimli","sequence":"first","affiliation":[{"name":"Institute for Nutrition Research University of Oslo P.O. Box 1046, Blindern Oslo 0316 Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camilla","family":"Giske","sequence":"additional","affiliation":[{"name":"Institute for Nutrition Research University of Oslo P.O. Box 1046, Blindern Oslo 0316 Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soheil","family":"Naderi","sequence":"additional","affiliation":[{"name":"Institute for Medical Biochemistry University of Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian A.","family":"Drevon","sequence":"additional","affiliation":[{"name":"Institute for Nutrition Research University of Oslo P.O. Box 1046, Blindern Oslo 0316 Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin","family":"Hollung","sequence":"additional","affiliation":[{"name":"Institute for Nutrition Research University of Oslo P.O. Box 1046, Blindern Oslo 0316 Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,8]]},"reference":[{"key":"e_1_2_2_2_1","first-page":"4139","article-title":"Cell Cycle Arrest and Apoptosis of Melanoma Cells by Docosahexaenoic Acid: Association with Decreased pRb Phosphorylation","volume":"60","author":"Albino A.P.","year":"2000","journal-title":"Cancer Res."},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1996.332"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401030"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/01635588909514002"},{"key":"e_1_2_2_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/130.10.2434"},{"key":"e_1_2_2_7_1","first-page":"1927","article-title":"Modulation of Experimental Colon Tumorigenesis by Types and Amounts of Dietary Fatty Acids","volume":"61","author":"Rao C.V.","year":"2001","journal-title":"Cancer Res."},{"key":"e_1_2_2_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11745-001-0765-x"},{"key":"e_1_2_2_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711050103"},{"key":"e_1_2_2_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/21.3.485"},{"key":"e_1_2_2_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1305"},{"key":"e_1_2_2_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80430-4"},{"key":"e_1_2_2_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)00553-X"},{"key":"e_1_2_2_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80434-1"},{"key":"e_1_2_2_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80501-2"},{"key":"e_1_2_2_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1322"},{"key":"e_1_2_2_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1309"},{"key":"e_1_2_2_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/35037710"},{"key":"e_1_2_2_19_1","first-page":"3976","article-title":"Specific Proteolytic Cleavage of Poly(ADP\u2010ribose) Polymerase: An Early Marker of Chemotherapy\u2010Induced Apoptosis","volume":"53","author":"Kaufmann S.H.","year":"1993","journal-title":"Cancer Res."},{"key":"e_1_2_2_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/371346a0"},{"key":"e_1_2_2_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008044200"},{"key":"e_1_2_2_22_1","first-page":"6811","article-title":"Tumor\u2010Induced Apoptosis of T Cells: Amplification by a Mitochondrial Cascade","volume":"60","author":"Gastman B.R.","year":"2000","journal-title":"Cancer Res."},{"key":"e_1_2_2_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)02268-2"},{"key":"e_1_2_2_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201131"},{"key":"e_1_2_2_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.42.26159"},{"key":"e_1_2_2_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.10028"},{"key":"e_1_2_2_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.25.15628"},{"key":"e_1_2_2_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.32.22686"},{"key":"e_1_2_2_29_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2000.4839"},{"key":"e_1_2_2_30_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.15.1899"},{"key":"e_1_2_2_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/42867"},{"key":"e_1_2_2_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006676-200105000-00004"},{"key":"e_1_2_2_33_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.27447"},{"key":"e_1_2_2_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-4644(20010401)81:1<128::AID-JCB1029>3.0.CO;2-G"},{"key":"e_1_2_2_35_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3360451"}],"container-title":["Lipids"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aocs.onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s11745-002-0963-6","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T09:11:29Z","timestamp":1760951489000},"score":1,"resource":{"primary":{"URL":"https:\/\/aocs.onlinelibrary.wiley.com\/doi\/10.1007\/s11745-002-0963-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,8]]},"references-count":34,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2002,8]]}},"alternative-id":["10.1007\/s11745-002-0963-6"],"URL":"https:\/\/doi.org\/10.1007\/s11745-002-0963-6","archive":["Portico"],"relation":{},"ISSN":["0024-4201","1558-9307"],"issn-type":[{"value":"0024-4201","type":"print"},{"value":"1558-9307","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,8]]},"article-number":"797"}}