William L. Redmond
Date of Award
Bachelor of Science (B.S.) in Biology and University Honors
Vitamin E -- Derivatives, Apoptosis, Active oxygen -- Physiological effect, Cancer, Major histocompatibility complex
α-tocopherol ether linked acetic acid (α-TEA) is a Vitamin E derivative with antineoplastic and anti-metastatic properties, tumor specificity, and immunogenic characteristics. The compound is structurally similar to vitamin E, however a key difference is that it doesn’t retain any antioxidant properties. Interestingly, orally administered α-TEA appears to stimulate anti-tumor immunity, which, along with its anti-metastatic and antineoplastic properties, makes the molecule’s mechanism of action worth investigating. Due to the loss of its anti-oxidative properties, the production of reactive oxygen species (ROS) and the cell viability of murine and human cancer cells treated with α-TEA, was analyzed over time. To determine the role that ROS play in inducing cell death, tumor cells were treated with α-TEA in the presence of reduced L-Glutathione (GSH), or the soluble form of vitamin E (TPGS; D-α-tocopheryl polyethylene glycol succinate). We also assessed the mechanism by which α-TEA affected cell death by screening for the expression of Major Histocompatibility Complex (MHC) Class I and II and the non classical MHC protein CD1d, as well as that of cell surface markers associated with immunogenic cell death (ICD), such as calreticulin. Surprisingly, our data revealed that α-TEA treatment induced ROS, but that cell death was only reduced when utilizing TPGS as an antioxidant, and not when GHS was present. Further analysis revealed that α-TEA doesn’t induce ICD in all tumor cells, but may do so in certain cell lines. Overall, our findings support the hypothesis that α-TEA induces apoptosis in cancer cells through ROS build up, and that when this pathway is blocked, these ROS will initiate death through the formation of the Mitochondrial Permeability Transition Pore (MPTP), or damage to the rough Endoplasmic Reticulum.
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Barragan Echenique, Diego Mathias, "α-TEA's Tumor Toxicity may be Attributed to its Capability of Inducing Oxidative Damage in the Endoplasmic Reticulum" (2015). University Honors Theses. Paper 124.