IMR Press / FBL / Volume 12 / Issue 6 / DOI: 10.2741/2206

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Alpha-tocopheryl phosphate is a novel apoptotic agent
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1 Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, 1901 Perdido St., Suite 7103, New Orleans, LA. 70112-1393, USA
2 Department of Pharmacology and Toxicology, Faculty of Medicine, Universiteit Maastricht, P.O. Box 616, NL 6200 MD Maastricht, The Netherlands
3 Department of Medical Oncology, Vrije Universiteit Medical Center, De Boelelaan 1117, NL 1081 HV Amsterdam, The Netherlands
Front. Biosci. (Landmark Ed) 2007, 12(6), 2013–2019;
Published: 1 January 2007

Alpha-tocopheryl succinate (TOS) is a well-known potent and selective apoptotic agent. This apoptotic activity has been ascribed to its detergent-like property which is also shared by the structurally related compound, alpha-tocopheryl phosphate (TOP). TOP meets the structural requirements that have been described for the apoptotic activity of TO esters, i.e. the combination of three structural, one functional, one signalling and one hydrophobic domain. In this study, we have investigated the effect of TOP on the osteosarcoma cell line MG-63 using TOS as a reference compound. As compared with TOS, TOP showed a higher proliferative and apoptosis inducing activity on the MG-63 cancer cell line. The cytotoxic effect of TOP and TOS seems to be due to the effect of the intact compounds, since only a minor conversion into alpha-tocopheryl (TO) could be detected. EPR experiments showed that TOS and TOP reduced membrane fluidity, whereas TO had no effect. In addition, induction of erythrocyte hemolysis by TOP depended on the pH. These results suggest that the detergent-like activity of these compounds might be involved in their biological effect. Due to the potent biological activities, TOP might be clinically useful.

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