Natural alkylglycerols restrain growth and metastasis of grafted tumors in mice.
Alkylglycerols are natural etherlipids abundant in shark liver oil (SLO) in a diacylated form. SLO is known to have antitumor properties and was recently described as an inhibitor of tumor neovascularization. However, most studies did not discriminate between the respective activities of alkylglycerols and of fatty acids, which both have potent biological properties. In this work, a mouse model was used to investigate the antitumor effects of SLO and of alkylglycerols purified from the same source, both administered orally. We demonstrated that either pure alkylglycerols or SLO reduced the tumor growth in a similar manner, suggesting that alkylglycerols were involved in this effect. In alkylglycerol-treated mice, metastasis dissemination was reduced by 64 +/- 8%, whereas SLO effect was 30 +/- 9% below control. Purified alkylglycerols also decreased significantly plasmalogen content in tumors, whereas SLO had no such effect. Finally, we demonstrated that a 5-day treatment with alkylglycerols curtailed the presence in tumors of von Willebrand factor, a marker of endothelial cells. This result suggested an anti-angiogenic effect of alkylglycerols. In summary, alkylglycerols were shown to decrease the growth, vascularization, and dissemination of Lewis lung carcinoma tumors in mice. These findings suggest that the antitumor activity of SLO is likely mediated by the presence of alkylglycerols.
Pedrono
Frederique
F
Laboratoire de Pharmacologie Moléculaire, Faculté de Pharmacie, Rennes, France.
Martin
Bénédicte
B
Leduc
Christine
C
Le Lan
Jacky
J
Saïag
Bernard
B
Legrand
Philippe
P
Moulinoux
Jacques-Philippe
JP
Legrand
Alain B
AB
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D005395:Fish Oils / Q000737:chemistry* / Q000494:pharmacology; D005990:Glycerol / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D012754:Sharks; D014407:Tumor Cells, Cultured; D014841:von Willebrand Factor
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D005395:Fish Oils; D014841:von Willebrand Factor; D005990:Glycerol