Which alkylglycerols from shark liver oil have anti-tumour activities?
Alkylglycerols (alkyl-Gro) are ether lipids abundant in shark liver oil (SLO), and oral SLO or alkyl-Gro mix from this source have several in vivo biological activities including stimulation of haematopoiesis an immunological defences, or anti-tumour and anti-metastasis activities in vivo. Composition of natural alkyl-Gro mix contains several alkyl-Gro varying by chain length and unsaturation, and individual anti-tumour activity of each molecule present in natural mix remained unknown. We synthesized six prominent constituents of natural alkyl-Gro mix, namely 12:0, 14:0 16:0, 18:0, 16:1 n-7, and 18:1 n-9 alkyl-Gro. Using an in vivo model of grafted tumour in mice (3LL cells), we studied and compared the oral anti-tumour and anti-metastasis activities of each of these 6 alkyl-Gro. 16:1 and 18:1 alkyl-Gro showed strong activity in reducing lung metastasis number, while saturated alkyl-Gro had weaker (16:0) or no (12:0, 14:0, 18:0) effect. Spleen weights at day 20 after graft were also measured and showed tremendous variations depending on the treatment. Tumour graft resulted in a raise in spleen weight in control group, this raise was nearly abolished in 16:1 and 18:1 alkyl-Gro-treated mice, and was reduced in 14:0 and 16:0 alkyl-Gro-treated mice. Conversely, 18:0 alkyl-Gro-treated mice showed spleen weigh raise as compared with untreated grafted mice. These new data demonstrate a prominent role of unsaturation in the anti-tumour activities of alkyl-Gro.
Deniau
Anne-Laure
AL
Laboratoire de Pharmacologie Moléculaire, Université de Rennes 1, France.
Mosset
Paul
P
Le Bot
Damien
D
Legrand
Alain B
AB
D000284:Administration, Oral; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000138:chemical synthesis*; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage* / Q000737:chemistry*; D005990:Glycerol / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D006801:Humans; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology; D008099:Liver / Q000737:chemistry; D008175:Lung Neoplasms / Q000178:diet therapy* / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009368:Neoplasm Transplantation; D009929:Organ Size; D012754:Sharks; D013154:Spleen / Q000473:pathology; D013552:Swine; D014407:Tumor Cells, Cultured
D018906:Antineoplastic Agents, Alkylating; D005395:Fish Oils; D008055:Lipids; D005990:Glycerol