vitamin e succinate

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Clin Cancer Res. 2002 Mar;8(3):863-9.

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.
====================================================================

Weber T, Lu M, Andera L, Lahm H, Gellert N, Fariss MW, Korinek V,
Sattler W, Ucker DS, Terman A, Schröder A, Erl W, Brunk UT, Coffey RJ,
Weber C, Neuzil J.

Institute for Prevention of Cardiovascular Diseases, Ludwig
Maximilians University, Munich, 80336 Germany.

Alpha-tocopheryl succinate (alpha-TOS), a redox-inactive analogue of
vitamin E, is a strong inducer of apoptosis, whereas alpha-tocopherol
(alpha-TOH) lacks apoptogenic activity (J. Neuzil et al., FASEB J.,
15: 403-415, 2001). Here we investigated the possible antineoplastic
activities of alpha-TOH and alpha-TOS and further explored the
potential of alpha-TOS as an antitumor agent. Using nude mice with
colon cancer xenografts, we found that alpha-TOH exerted modest
antitumor activity and acted by inhibiting tumor cell proliferation.
In contrast, alpha-TOS showed a more profound antitumor effect, at
both the level of inhibition of proliferation and induction of tumor
cell apoptosis. alpha-TOS was nontoxic to normal cells and tissues,
triggered apoptosis in p53(-/-) and p21(Waf1/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, alpha-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.

PMID: 11895920 PubMed - indexed for MEDLINE

Publication Types, MeSH Terms, Substances
-----------------------------------------

Publication Types:

Comparative Study

Research Support, Non-U.S. Gov't

MeSH Terms:

Animals

Antineoplastic Agents/pharmacology

Apoptosis/drug effects

Apoptosis Regulatory Proteins

Caspases/metabolism

Colonic Neoplasms/drug therapy

Colony-Forming Units Assay

Cyclin-Dependent Kinase Inhibitor p21

Cyclins/metabolism

Drug Synergism

Humans

Membrane Glycoproteins/metabolism

Mice

Myocardial Contraction/drug effects

Myocardial Contraction/physiology

Myocardium/cytology

Neoplasm Invasiveness

TNF-Related Apoptosis-Inducing Ligand

Tocopherols

Transfection

Tumor Cells, Cultured/drug effects

Tumor Necrosis Factor-alpha/metabolism

Tumor Suppressor Protein p53/metabolism

Vitamin E/analogs & derivatives

Vitamin E/pharmacology

Xenograft Model Antitumor Assays

alpha-Tocopherol/pharmacology

Substances:

Antineoplastic Agents

Apoptosis Regulatory Proteins

CDKN1A protein, human

Cdkn1a protein, mouse

Cyclin-Dependent Kinase Inhibitor p21

Cyclins

Membrane Glycoproteins

TNF-Related Apoptosis-Inducing Ligand

TNFSF10 protein, human

Tnfsf10 protein, mouse

Tumor Necrosis Factor-alpha

Tumor Suppressor Protein p53

Vitamin E

Tocopherols

alpha-Tocopherol

Caspases

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Molecular Biology Databases:

VITAMIN E - HSDB

Supplemental Content
--------------------

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Related articles
----------------

Elimination of hepatic metastases of colon cancer cells via
 p53-independent cross-talk between irinotecan and Apo2
 ligand/TRAIL.

Cancer Res. 2004 Dec 15; 64(24):9105-14.

Cancer Res. 2004

Alpha-tocopheryl succinate and TRAIL selectively synergise in
 induction of apoptosis in human malignant mesothelioma cells.

Br J Cancer. 2004 Apr 19; 90(8):1644-53.

Br J Cancer. 2004

ReviewVitamin E analogues as inducers of apoptosis: implications
 for their potential antineoplastic role.

Redox Rep. 2001; 6(3):143-51.

Redox Rep. 2001

Apoptosis induction in prostate cancer cells and xenografts by
 combined treatment with Apo2 ligand/tumor necrosis factor-related
 apoptosis-inducing ligand and CPT-11.

Cancer Res. 2003 Aug 1; 63(15):4713-23.

Cancer Res. 2003

ReviewVitamin E succinate and cancer treatment: a vitamin E
 prototype for selective antitumour activity.

Br J Cancer. 2003 Nov 17; 89(10):1822-6.

Br J Cancer. 2003

» See reviews...  » See all...

Cited by 10 PubMed Central articles
-----------------------------------

Alpha-tocopheryl succinate potentiates the paclitaxel-induced
 apoptosis through enforced caspase 8 activation in human H460 lung
 cancer cells.

Lim SJ, Choi MK, Kim MJ, Kim JK. Exp Mol Med. 2009 Oct 31;
41(10):737-45.

Exp Mol Med. 2009

TRAIL and Taurolidine induce apoptosis and decrease proliferation
 in human fibrosarcoma.

Daigeler A, Brenzel C, Bulut D, Geisler A, Hilgert C, Lehnhardt M,
Steinau HU, Flier A, Steinstraesser L, Klein-Hitpass L, et al. J
Exp Clin Cancer Res. 2008 Dec 12; 27:82. Epub 2008 Dec 12.

J Exp Clin Cancer Res. 2008

Alpha-tocopheryl succinate induces apoptosis by targeting
 ubiquinone-binding sites in mitochondrial respiratory complex II.

Dong LF, Low P, Dyason JC, Wang XF, Prochazka L, Witting PK,
Freeman R, Swettenham E, Valis K, Liu J, et al. Oncogene. 2008 Jul
17; 27(31):4324-35. Epub 2008 Mar 31.

Oncogene. 2008

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Vitamin E succinate is a potent novel antineoplastic agent with
 high selectivity and coope...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.

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