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Antitumor effect of a liposome-encapsulated β1,4-galactosyltransferase inhibitor.
International Journal of Pharmaceutics 2018 December 2
Galactosyltransferases are a family of enzymes responsible for the synthesis of glycan chains which are involved in cell proliferation, adhesion and apoptosis. A recently synthesized galactosyltransferase inhibitor, 2-naphthyl 2-butanamido-2-deoxy-1-thio-β-D-glucopyranoside (612), has been found to selectively inhibit β1,4-galactosyltransferase over β1,3-galactosyltransferase and, therefore, has potential to suppress the synthesis of cancer associated epitopes. However, the application of this inhibitory activity in biological systems remains unknown. In this study, 612 was introduced into a cationic liposome (LP) delivery system, and the anti-proliferative effects of both free and the LP-incorporated 612 (612-LP) were investigated in A549 lung cancer cells, which actively express anionic sialic acid moieties on the surfaces of cells. The anti-proliferative effects were evaluated via MTT assays. The results revealed that free 612 and empty LP impose neither anti-proliferative nor apoptotic effects on cancer cells at low doses, whereas the 612-LP system inhibited cancer cell growth at a concentration as low as 0.1 μg/mL after 3 days of incubation, suggesting that this formulation enabled efficient delivery of 612 into cells and promoted the anti-proliferative activity of 612 against cancer cells. Therefore, this highly specific inhibitor 612 has the potential for development as an effective anti-cancer agent and merits further investigation.
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