Induction of Apoptosis in Human Breast Cancer Cells by 
Tocopherols and Tocotrienols



Ann's NOTE: Also look at the section called Information by Cancer Type. Remember vitamins are meant to be used in combination. Especially the antioxidants (E, C, selenium, A, beta-carotene, etc).

HSI (Health Science Institute) panelist Allan Spreen, M.D., "Any nutritional doc who knows anything at all knows not to use alpha tocopherol, natural or otherwise, because using the alpha fraction without the other fractions - beta, delta, and gamma - causes the other fractions to decrease in value. This is why good supplements are always of the 'mixed tocopherol' variety, containing all the fractions".

How an increased intake of alpha-tocopherol can suppress the bioavailability of gamma-tocopherol.

Wolf G.

Department of Nutritional Sciences and Toxicology, University of California, Berkeley, USA. ilsipress@ilsi.org

alpha-Tocopherol is the only form of vitamin E in vitamin supplements, whereas gamma-tocopherol is the predominant form of vitamin E in the US diet. gamma-Tocopherol has beneficial properties as an anti-inflammatory and possibly anti-atherogenic and anticancer agent.

Excess a-tocopherol taken in supplements causes a reduction of gamma-tocopherol concentration in plasma. The biochemical mechanism of this effect, which is important to human nutrition, has recently been elucidated.

Nutr Rev. 2006 Jun;64(6):295-9.



VITAMIN E AND CANCER

by Abram Hoffer, M.D., PhD.

Vitamin E includes the tocopherols of which d-alpha tocopherol is the most active.

It is the major lipid soluble antioxidant protecting the polyunsaturated fatty acids (PUFA) in membranes against peroxidation.

The usual intake is about 12 IU/day. Peroxidation of the PUFA causes membrane damage. Vitamin E has other protective properties.

It destroys nitrite, which has been shown to increase the incidence of cancer.

It protects the red blood cells in lungs against the toxic effect of ozone and hydroxyl radical toxicity. Thus it has been shown to have a weak protective effect against some of the cancers (1)

More recent studies have shown an inverse relationship between levels of Vitamin E in blood and the development of cancer.

One study (2) compared the vitamin E levels in 289 patients with cancer of the colon and rectum against 1267 matched controls.

The E levels were slightly lower in the cancer cases. Similar findings were reported by Knekt (3), Palan et al., (4), and de Vries, et al (5). Knekt and colleagues (6) examined alpha-tocopherol levels in 36,2675 adults in Finland.

After eight years there were 766 cases of cancer. Persons with low levels had 1 1/2 times the chance of getting cancer compared to the highest level.

The association was strongest with gastrointestinal cancers and for other cancers not related to smoking. LeGardeur et al (7) concluded from their data that vitamin E deficiency may be associated with lung cancer and to a greater degree than vitamin A.

Thus the association between cancer and vitamin E consumption and cancer is not strong, but an increasing number of reports appear showing that there is some connection.

When so many variables are involved it is very difficult to find very high correlations between the condition and the effect of only one of the nutrients.

As long as we can not be sure what are the most effective cancer preventive agents and therapeutic compounds it seems only prudent to ensure that the subjects are obtaining enough vitamin E.

The main question is how much is enough.

Certainly the role of the RDA's is being seriously questioned by many and recommendations have been made that for each disease there may be unique RDA.

Literature Cited:

(1) Comstock, G.W. Helzlsouer, K.H. and Bush, T.L. Prediagnostic serum levels of carotenoids and vitamin E as related to subsequent cancer in Washington County, Maryland. Am. J. Clin. Nutr. 53: 260 S - 264 S, 1991.

(2) Longnecker, M.P. Martin-Morreno, J.M. Knekt,P. Nomura, A.M. Schober,S.E. St:ahelin,H.B. Wald, N.J. Gey, K.F. and Willett, W.C. Serum alpha-tocopherol concentrations in relation to subsequent colorectal cancer: pooled data from five cohorts. J. Nat Can Institute 84; 430-435, 1992.

(3) Knekt, P. Role of vitamin E in the prophylaxis of cancer. Annals of Medicine 23; 3 - 12, 1991.

(4) Palan, P.R. Mikhail, M.S. and Romney, S.L. Plasma levels of antioxidant beta-carotene and alpha-tocopherol in uterine cervix dysplasia and cancer. Nutrition and Cancer 15; 13 - 20, 1991.

(5) de Vries, N and Snow, G.B. Relationship of vitamins A and E and beta-carotene serum levels to head and neck cancer patients with and without second primary tumors. European Archives Oto-rhino-laryngology 247; 368-370, 1990.

(6) Knekt, P. Aromaa, A. Maatela, J. Aaran, R.K. Nikkara, T. Hakama, M. Hakulinen, T. Peto, R. and Teppo,L. Vitamin E and cancer prevention. American Journal of Clinical

Nutrition 53, 283S-286S, 1991.

(7) LeGardeur,B.Y., Lopez, A. and Johnson, W.D. A case-control study of serum vitamins A,E, and C in lung cancer patients. Nutrition and Cancer 14; 133-140, 1990.

More information by Dr. Hoffer about cancer treatment:

http://www.doctoryourself.com/cancer_hoffer.html

Details of a natural adjunctive cancer therapy:

http://www.doctoryourself.com/cancer.html


Vitamin E Succinate

A few studies on Vitamin E succinate -this group breast cancer issues

D-Alpha Tocopheryl Succinate
Vitamin E Succinate-Prostate
Succinate Induces Bca Cells to Undergo Differentiation
Free Radical Fighter
Succinate & DNA Synthesis Arrest MDA-MB-4356 Cells
alpha-Tocopheryl Succinate:A Review /Rads support
Vit E Succinate Promotes BCa Tumor Dormancy
Vit E Succinate Inhibits Colon Ca Liver Mets
alpha-Tocopherol Succinate Inhibits Gastric Ca Cells
Vit E succinate & Cancer Treatment
Alpha-tocoph succinate & TRAIL for Mesothelioma
Vit E: Mech of Action as Tumor Cell Growth Inhibitors

Journal of Nutrition, 2001

Vit E and Cysteine Peptidase Inhibitors:Rat Bca
Liposomal Formulated-dl-alpha Tocopherol :Mammary Tumor
Vitamin E (d-alpha-tocopherol succinate) & Radiation

Nutr Cancer, 1999

Antioxidant-free Diet Slows Tumor Growth in Mice

Experimental Biology 2001 Study shows negative results for Vitamins E and A

Oxidant-Antioxidant Status & Survival (Vit E)
Vitamin E Inhibits BCa Cell Proliferation with ER+
Defense of Vitamin E from Life Extension Foundation

June 2001 (response to J Am Med Assoc study)

Vitamin E Reduces Chromosomal Damage/Inhibits Hepatic Tumor (mice

Proc. Nat'l Acad Sci, 2/2000

Transforming Growth Factor alpha in Mice
Gamma Tocopherol Inhibits COX2

Proc Natl. Acad Sci, 10/00

Involvement of Activator Protein-1 & Apoptosis Vitamin E Succinate

Mol Carcino, July 97

Vit E Analogues Inducers of Apoptosis
Nicotine Inhibits Vit E Succinate-induced Apoptosis:Head/Neck
Oxidant-Antioxidant Status & Survival Bca

Int J Cancer, 2/02

Vitamin E Suppresses PSA expression (& more)

Proceedings of the National Academy of Sciences, 5/02

Doxirubicin/Vit E/Fish Oil (Mice)

From the Moss Reports, 10/02 Natl Univ of Singapore study

Dietary Alpha-Tocopherol Decreases A-Tocotrienol Not Gamma

J Nutr, 2/03

Tocotrienols
Tocotrienol-rich Fraction from Rice Bran Oil & Hepatocarc (rats)
Tocotrienols inhibit growth human breast ca cells irrespective of ER status.
Vit E Neuroprotective w/Cisplatin

JCO, 3.03

Ralph Moss' Take on this study
More Studies Show Vit E Protects From Cisplatin/Neurotox
Mice, Human Melanoma, Cisplatin & Alpha-tocopherol
Cisplatin & Anti–4-1BB: Synergistic Anticancer Effects
Pentoxifylline & Vit E Regresses RTx-Induced Fibrosis

J Clin Oncol, 7/03 Treatment after Radiation

Alpha-tcphrl & Ascrb Acid, Retinds/CigSmoke

J Nutr, 2/04

Vitamin E and Cardiac Disease

Washington Times, 12/04

Andrew Weil on Vitamin E and Heart Disease
Vitamin E: Safe, Effective, and Heart-Healthy
Vitamin E

Purdue News Service, 12/04

Vit E Reduces Risk of More Advanced Disease
Alpha-tea (Vit E derivative) Stops Mets in Mice (Food)

Cancer Research, 10/06 AACR Press Release

In Vivo Angiogenesis Suppressed by Unsatrtd Vit E Tocotrienol

J. Nutr, August 2007


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