Natural Alkylglycerols Restrain Growth and Metastasis of Grafted Tumors in Mice

Abstract

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.

Ether lipids

“…Indeed, a recent study revealed that downregulation of PKC-␤ isoform hampered tumour development in endothelial cells via strong inhibition of angiogenesis in mice (Yoshiji et al, 1999), thus, denoting the possible antineoplastic action of alkylglycerol via PKC inhibition implicated in reduced tumour vascularisation. Remarkably, alkylglycerols have been reported to be responsible for both the anti-tumour and anti-angiogenic properties of shark liver oil in Lewis lung carcinoma cells in mice (Pedrono et al, 2004). In addition, the same study showed that alkylglycerols increased the permeability of endothelial cells, presumably by changes in the cytoskeleton and cell-to-cell adhesion, that could be involved in tumour growth inhibition.…”

“…These results indicate that 1-O-alkylglycerols are effective adjuvants for the antigen Ova (Acevedo et al, 2006). Pedrono et al have investigated the effect of alkylglycerols (isolated from shark liver oil) and shark liver oil (containing about 25% DAGE and deprived of squalene) on tumour growth, pulmonary metastasis and vascularisation of Lewis lung carcinoma (3LL) cells grafted in mice (Pedrono et al, 2004). The results showed that both the shark liver oil and the mixture of natural alkylglycerols reduced the 3LL-grafted carcinoma up to similar percentages, 29 and 26%, respectively, compared to controls.…”

Synthesis and biological properties of the fluorescent ether lipid precursor 1-O-[9′-(1″-pyrenyl)]nonyl-sn-glycerol

“…This may be linked to the inhibition of protein kinase C (28). Also, alkylglycerol treatment resulted in decreased cancer cell reproduction and a reduced ability of the cancer cells to metastasize (29). It is not clear whether HG or a metabolite (acylated or phosphorylated) is responsible for these effects.…”

The effect of shark liver oil on the tumor infiltrating lymphocytes and cytokine pattern in mice

“…Alkylglycerols have immunostimulatory action on macrophages and result in increase in leukocyte and thrombocyte counts (Hasle and Rose, 1991;Pugliese et al, 1998). Alkylglycerols have also anti-angiogenic effect and the anti-tumor activity of SLO is likely mediated by the presence of alkylglycerols (Pedrono et al, 2004).…”