Growth inhibitory effect of lithium gammalinolenate on pancreatic cancer cell lines: the influence of albumin and iron.
Essential fatty acids, especially gamma linolenic (GLA) and eicosapentaenoic acids, have been proposed as potential anticancer drugs. Our aim was to study the effect of the lithium salt of gamma linolenic acid (LiGLA) on the growth of two human pancreatic cancer cell lines (MIA PaCa2 and Panc 1) and primary human fibroblasts (HFF 5) in vitro. Cell growth was assessed by a microculture tetrazolium (MTT) assay. LiGLA had a selective growth inhibitory effect on pancreatic cancer cell lines with 50% growth inhibition (IC50) at approximately 6-16 mumol/l compared with approximately 111 mumol/l for the fibroblasts. The degree of growth inhibition increased with the time of exposure to LiGLA. Special attention was paid to the influence of albumin and iron on LiGLA-mediated growth inhibition. Albumin incorporated into essentially serum-free culture medium inhibited the effect of LiGLA in a dose-dependent manner, associated with reduced GLA uptake by cancer cells. Ferric ions were confirmed as potentiators of the growth inhibitory effect of LiGLA but more physiologically relevant transferrin-bound iron was ineffective. With further improvements in the fatty acid delivery mechanism, LiGLA may become a useful adjunct in the management of pancreatic cancer patients.
Ravichandran
D
D
University Surgical Unit, Southampton General Hospital, UK.
Cooper
A
A
Johnson
C D
CD
D000418:Albumins / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002712:Chlorides; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005290:Ferric Compounds / Q000494:pharmacology*; D006801:Humans; D018020:Lithium Compounds / Q000378:metabolism / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D017965:gamma-Linolenic Acid / Q000378:metabolism / Q000627:therapeutic use*
D000418:Albumins; D002712:Chlorides; D005290:Ferric Compounds; D018020:Lithium Compounds; D017965:gamma-Linolenic Acid; C024555:ferric chloride