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  • Title: Vitamin E succinate in combination with mda-7 results in enhanced human ovarian tumor cell killing through modulation of extrinsic and intrinsic apoptotic pathways.
    Author: Shanker M, Gopalan B, Patel S, Bocangel D, Chada S, Ramesh R.
    Journal: Cancer Lett; 2007 Sep 08; 254(2):217-26. PubMed ID: 17449172.
    Abstract:
    Adenovirus-mediated mda-7 (Ad-mda7) gene transfer has been shown to induce apoptosis in various human cancer cells while sparing normal cells. Vitamin E succinate (VES) is also known to exhibit antitumor activity against a number of human cancer cell lines. We hypothesized that a combination of the two agents would produce an enhanced antitumor effect in MDAH2774 human ovarian cancer cells. Treatment of MDAH2774 cells with Ad-mda7 plus VES resulted in enhanced antitumor activity that involved the activation of two apoptotic pathways. Activation of the extrinsic pathway was demonstrated by increased cell-surface Fas expression and cleavage of Bid and caspase-8. Activation of the intrinsic pathway was demonstrated by disruption of mitochondrial potential; and activation of downstream capase-9 and caspase-3 via cytochrome C release. In contrast, the combination of Ad-mda7 plus VES did not show any antitumor activity against normal fibroblasts, indicating selective tumor cell killing. Our in vitro results provide a basis for further preclinical testing of Ad-mda7 plus VES as a potential cancer treatment strategy.
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