Alpha-Tocopheryl succinate: Toxicity and lack of anti-tumour activity in immuno-competent mice

Alpha-tocopheryl succinate (α-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 α-TOS treatment in our immuno-competent and syngeneic murine mesothelioma model. VitE analogues such as α-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 α-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 α-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 α-TOS requires careful consideration.