Vitamin E succinate is a potent novel antineoplastic agent with high selectivity and cooperativity with tumor necrosis factor-related apoptosis-inducing ligand (Apo2 Ligand) in vivo
Author(s)
Weber, T
Lu, M
Andera, L
Lahm, H
Gellert, N
Fariss, MW
Korinek, V
Sattler, W
Ucker, DS
Terman, A
Schroder, A
Erl, W
Brunk, UT
Coffey, RJ
Weber, C
Neuzil, J
Griffith University Author(s)
Year published
2002
Metadata
Show full item recordAbstract
a -Tocopheryl succinate (a -TOS), a redox-inactive analogue of vitamin E, is a strong inducer of apoptosis, whereas -tocopherol (a -TOH) lacks apoptogenic activity (J. Neuzil et al., FASEB J., 15: 403-415, 2001). Here we investigated the possible antineoplastic activities of a -TOH and a -TOS and further explored the potential of -TOS as an antitumor agent. Using nude mice with colon cancer xenografts, we found that a -TOH exerted modest antitumor activity and acted by inhibiting tumor cell proliferation. In contrast, a -TOS showed a more profound antitumor effect, at both the level of inhibition of proliferation and induction ...
View more >a -Tocopheryl succinate (a -TOS), a redox-inactive analogue of vitamin E, is a strong inducer of apoptosis, whereas -tocopherol (a -TOH) lacks apoptogenic activity (J. Neuzil et al., FASEB J., 15: 403-415, 2001). Here we investigated the possible antineoplastic activities of a -TOH and a -TOS and further explored the potential of -TOS as an antitumor agent. Using nude mice with colon cancer xenografts, we found that a -TOH exerted modest antitumor activity and acted by inhibiting tumor cell proliferation. In contrast, a -TOS showed a more profound antitumor effect, at both the level of inhibition of proliferation and induction of tumor cell apoptosis. a -TOS was nontoxic to normal cells and tissues, triggered apoptosis in p53-/- and p21Waf1/Cip1(-/-) cancer cells, and exerted a cooperative proapoptotic activity with tumor necrosis factor-related apoptosis-inducing ligand (Apo2 ligand) due to differences in proapoptotic signaling. Finally, a -TOS cooperated with tumor necrosis factor-related apoptosis-inducing ligand in suppression of tumor growth in vivo. Vitamin E succinate is thus a potent and highly specific anticancer agent and/or adjuvant of considerable therapeutic potential.
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View more >a -Tocopheryl succinate (a -TOS), a redox-inactive analogue of vitamin E, is a strong inducer of apoptosis, whereas -tocopherol (a -TOH) lacks apoptogenic activity (J. Neuzil et al., FASEB J., 15: 403-415, 2001). Here we investigated the possible antineoplastic activities of a -TOH and a -TOS and further explored the potential of -TOS as an antitumor agent. Using nude mice with colon cancer xenografts, we found that a -TOH exerted modest antitumor activity and acted by inhibiting tumor cell proliferation. In contrast, a -TOS showed a more profound antitumor effect, at both the level of inhibition of proliferation and induction of tumor cell apoptosis. a -TOS was nontoxic to normal cells and tissues, triggered apoptosis in p53-/- and p21Waf1/Cip1(-/-) cancer cells, and exerted a cooperative proapoptotic activity with tumor necrosis factor-related apoptosis-inducing ligand (Apo2 ligand) due to differences in proapoptotic signaling. Finally, a -TOS cooperated with tumor necrosis factor-related apoptosis-inducing ligand in suppression of tumor growth in vivo. Vitamin E succinate is thus a potent and highly specific anticancer agent and/or adjuvant of considerable therapeutic potential.
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Journal Title
Clinical Cancer Research
Volume
8
Issue
3
Publisher URI
Copyright Statement
© 2002 AACR. Please refer to the journal link for access to the definitive, published version.
Subject
Oncology and carcinogenesis