Effect of 1-(gamma)linolenyl-3-eicosapentaenoyl propane diol on the growth of human pancreatic carcinoma in vitro and in vivo.
Essential fatty acids such as (gamma)linolenic (GLA) and eicosapentaenoic (EPA) acids have been proposed as anticancer drugs. The aim of this study was to test the effect of a lipid emulsion containing both GLA and EPA in a novel chemical formulation of 1-(gamma)linolenyl-3-eicosapentaenoyl propane diol on the growth of human pancreatic carcinoma in vitro and in nude mice. This compound had a dose-dependent growth-inhibitory effect on human pancreatic cancer cell lines MIA PaCa-2 and Panc-1 in vitro. The concentration necessary for 50% growth inhibition was 25 micromol/l for MIA PaCa-2 and 68 micromol/l for Panc-1 (95% CI 20-29 and 59-77 micromol/l respectively). Nude mice bearing subcutaneous pancreatic tumours produced with the MIA PaCa-2 cell line were treated with the maximum tolerated dose (6.75 mg GLA and 7.3 mg EPA per g of body weight) administered over 10 days by daily intravenous (i.v.) bolus injections. No antitumour effect or major alteration in tumour lipid fatty acid composition was seen in comparison with control animals. Concurrent treatment with parenteral iron (iron saccharate, 5 microg/gram body weight daily) did not make a significant difference. Further improvements in fatty acid delivery mechanisms are necessary before they can become useful anticancer agents.
Ravichandran
D
D
University Surgical Unit, Southampton General Hospital, Southampton, UK.
Cooper
A
A
Johnson
C D
CD
D000818:Animals; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004354:Drug Screening Assays, Antitumor; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018709:Statistics, Nonparametric; D014407:Tumor Cells, Cultured; D017965:gamma-Linolenic Acid / Q000627:therapeutic use*
D004338:Drug Combinations; D005227:Fatty Acids; D017965:gamma-Linolenic Acid; D015118:Eicosapentaenoic Acid; D007501:Iron