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University of Texas, US, Finds Tocotrienols at Low Levels, As a potent Natural Vitamin E to Induce Apoptosis (Cell Death) In Human Breast Cancer Cells

March 15th, 2000

In a recent (1999) publication in the prestigious journal of Nutrition and Cancer, researchers at the University of Texas, US, joined four other research institutions worldwide, in confirming that tocotrienols, especially the delta-tocotrienol, are potent inhibitor of human breast cancer cells by inducing cell death (apoptosis)in them.

Breast cancer is the most common cancer among women, excluding non-melanoma skin cancers. The American Cancer Society estimates that in the year 2000, about 182,800 new cases of invasive breast cancer (stage I - IV) will be diagnosed among women in the United States. Breast cancer also occurs in men. An estimated 14,000 cases will be diagnosed among men. The incidence of breast cancer has more than doubled over the past 30 years. In 1964, the lifetime risk was 1 in 20 women. Today, it is 1 in 8 women will develop breast cancer in her lifetime. It is sad to say that breast cancer is the most common cancer for women in the world.

The usual treatments for breast cancers are surgery, radiation therapy, hormone therapy and chemo-therapy. The drug, Tamoxifen is the widely used hormone therapy for women who already have breast cancers. The down side of Tamoxifen is that long-term treatment increases a woman¡¦s chance of three rare but serious health problems: endometrial cancer, pulmonary embolism (a blood clot in the lung) and deep vein thrombosis (a blood clot in a major vein).

Tocotrienol's ability to inhibit and induce the apoptosis of breast cancer cells, may be an additional natural way of supplement (in addition to the drug treatment, chemo and radiation therapy recommended by surgeon) for women who have developed breast cancer and for women who have a family history of breast cancer.

In the study carried out at the University of Texas, Austin, the apoptosis-inducing properties of natural RRR-α-, β-, γ-, δ-tocopherols, α-, γ-, δ-tocotrienols, RRR-α-tocopheryl acetate (vitamin E acetate) and RRR-ƒÑ-tocopheryl succinate (vitamin E succinate) were investigated in estrogen-responsive MCF7 and estrogen-nonresponsive MDA-MB-435 human breast cancer cell lines. Vitamin E succinate, a known inducer of apoptosis in several cell lines, including human breast cancer cells, served as a positive control. The results of the study found that estrogen-responsive MCF7 cells were more susceptible than the estrogen-nonresponsive MDA-MB-435 cells. Delta-tocotrienol was found be the most potent inducer of apoptosis in both types of human breast cancer cells and was twice as potent as gamma-tocotrienol in inducing apoptosis.

With the exception of RRR-δ-tocopherol, the tocopherols (alpha, beta and gamma-tocopherol) and RRR-α-tocopheryl acetate were ineffective in induction of apoptosis in both cell lines when tested within the range of their solubility, i.e., 10 - 200μg/ml.

In summary, these studies demonstrate that naturally occurring tocotrienols and delta-tocopherol are effective to induce cell deaths of human breast cancer cells, irrespective of estrogen receptor status. The ability of tocotrienols, especially delta-tocotrienol at low levels, to induce human breast cancer to undergo cell death, makes this compound a promising natural and side-effect free candidate for possible chemotherapeutic use.

Tocotrienol may be a new word to many. It sounds much like the more familiar ¡§tocopherol¡¨. Indeed, tocotrienols are related to tocopherols. Both tocotrienols and tocopherols are Vitamin E. Tocotrienols differ from tocopherols in their molecular structure only by having an unsaturated isoprenoid side chain. Tocopherols have saturated side chain, ie : lacking double bonds. Tocotrienols are widely distributed in the plant kingdom, with the highest concentration found in palm oil. They are also found in grains such as barley, rice bran, oats, etc. In comparison, delta-tocotrienol is found in significantly high level in the fruits of oil palm (highest in nature) but low or absent in other sources.

Possible clues to how tocotrienols inhibit cancer cell proliferation may be attributed to the following mechanisms 1. by reducing of protein kinase C activity in human breast cancer cells (Guthrie et al., 1997), 2. by affecting the tyrosine phosphorylation of the epidermal growth factor receptor (Carroll, et al.), 3. by suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate limiting enzyme for cholesterol synthesis (Elson & Qureshi et al., 1995). The Palm Oil Research Institute of Malaysia (PORIM) and Carotech have embarked on a double-blind clinical human study to determine possible therapeutic applications.

Individuals who are diagnosed with breast cancer may want to consider supplementing their diet with natural tocotrienols vitamin E as part of a long-term nutritional plan, in addition to the therapeutic treatments recommended by their physicians. Most of the palm tocotrienols supplements in the market contain typically 30 - 50mg of tocotrienols per capsules.

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