Alpha-Tocopheryl succinate: toxicity and lack of anti-tumour activity in immuno-competent mice.
Alpha-tocopheryl succinate (alpha-TOS), an analogue of vitamin E (VitE), inhibits peritoneal human malignant mesoethelioma xenograft development in immuno-compromised mice via the induction of apoptosis of tumour cells [Tomasetti, M., Gellert, N., Procopio, A., Neuzil, J., 2004. A vitamin E analogue suppresses malignant mesothelioma in a preclinical model: a future drug against a fatal neoplastic disease? Int. J. Cancer 109, 641-642]. We tested the effect of systemic alpha-TOS treatment in our immuno-competent and syngeneic murine mesothelioma model. VitE analogues such as alpha-TOS have been developed for clinical use as supplements mainly for the treatment of VitE deficiency and are considered safe and non-toxic when taken orally. In our murine model of mesothelioma alpha-TOS was not only ineffective at inhibiting established tumour development at the published doses, but resulted in severe side effects characterized by both behavioural changes, intra-peritoneal abnormalities and the destruction of T cells. Toxicity of alpha-TOS has not been reported to date perhaps due to a lack of studies conducted in fully immuno-competent hosts. Our results suggest that the translation of animal studies to clinical treatment with alpha-TOS requires careful consideration.
Ireland
Demelza J
DJ
Microbiology and Immunology (M502), School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, 35 Stirling Highway, 6009 Perth, Western Australia, Australia.
Kissick
Haydn T
HT
Beilharz
Manfred W
MW
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D007121:Immunocompetence; D008654:Mesothelioma / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D024505:Tocopherols; D017211:Treatment Failure; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000633:toxicity; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D000970:Antineoplastic Agents; D014810:Vitamin E; D024505:Tocopherols