Alpha-Tocopheryl succinate: Toxicity and lack of anti-tumour activity in immuno-competent mice
Tuesday, October 9th, 2007.
Food and Chemical Toxicology . 2007 Aug 29; [Epub ahead of print] [Link]
Ireland DJ, Kissick HT, Beilharz MW.
Microbiology and Immunology (M502), School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, 35 Stirling Highway, 6009 Perth, Western Australia, Australia.
Abstract
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.
Keywords: Mesothelioma; Animal model; Vitamin E; Toxicity; Anti-cancer therapy
Abbreviations: α-TOS, alpha-tocopheryl succinate; VitE, vitamin E; DMSO, dimethyl sulphoxide; TNF, tumour necrosis factor; TRAIL, TNF-related apoptosis-inducing ligand; FGFR1, fibroblast growth factor receptor-1; SEM, standard error of the mean; FACS, fluorescence activated cell sorting; s.c., subcutaneous; i.p., intra-peritoneal; ROS, reactive oxygen species; MM, malignant mesothelioma
Glossary
- therapy
- any of the measures taken to treat a disease. Unproven therapy is any therapy that has not been scientifically tested and approved. Use of an unproven therapy instead of standard (proven) therapy is called alternative therapy. Some alternative therapies have dangerous or even life-threatening side effects. For others, the main danger is that a patient may lose the opportunity to benefit from standard therapy. Complementary therapy, on the other hand, refers to therapies used in addition to standard therapy. Some complementary therapies may help relieve certain symptoms of cancer, relieve side effects of standard cancer therapy, or improve a patient's sense of well-being. The ACS recommends that patients considering use of any alternative or complementary therapy discuss this with their health care team.
- side effects
- effects of treatment (other than the effects on the cancer) such as hair loss caused by chemotherapy, and fatigue caused by radiation therapy.
- immunology
- (im-mune-ahl-o-jee) study of how the body resists infection and certain other diseases. Knowledge gained in this field is important to those cancer treatments based on the principles of immunology.
- cell
- the basic unit of which all living things are made. Cells replace themselves by splitting and forming new cells (mitosis). The processes that control the formation of new cells and the death of old cells are disrupted in cancer.
- cancer
- malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.
- mesothelioma
- a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.
- peritoneal
- (pair-uh-tuh-nee-al) the serous membrane that lines the cavity of the abdomen. (More on Peritoneal Mesothelioma.)
- apoptosis
- a type of cell death in which the cell basically commits suicide; scientists believe some types of cancer may originate from an interruption of this programmed cell death, allowing cells to grow out of control.
