Tocotrienols and cancer:

A natural form of vitamin E called alpha tocopheryl succinate, found in more expensive supplements, may provide some protection. In test tube studies, the alpha tocopheryl succinate form of vitamin E has been shown to inhibit breast cancer cell growth. [22-35]

It is the tocotrienols, however, that have demonstrated the most significant potential to not only reduce the incidence of breast cancer, but also to inhibit existing breast cancer cell propagation.

Tocotrienols have been shown to inhibit growth of estrogen receptor positive breast cancer cells by as much as 50% in culture.[36-39] In contrast, many studies have found that alpha tocopherol does not influence proliferation.[36,38-40] Even in studies where alpha tocopherol was shown effective against some breast cancer cell lines, the amount required for 50% growth inhibition was more than 20 times higher than the growth inhibitory concentrations of the tocotrienols.[37]

Comparison of multiple studies indicates that the growth inhibitory effects of alpha tocopherol wears off,[41] whereas limited data suggest that the growth inhibitory effects of the tocotrienols on breast cancer cells is maintained or increases with duration of exposure (in culture).[39,42]

It is interesting to note that the body naturally concentrates tocotrienols into breast adipose tissue. Based on studies done to date, it is likely that breast adipose tissue levels of tocotrienols will be 5 to 10 times greater than plasma.[48-50] This indicates that even lower tocotrienol supplementation might be adequate to saturate breast adipose tissue with the amount of tocotrienols that have inhibited breast cancer cell proliferation and induced apoptosis in culture.

A cardinal feature of breast tumors are rapidly proliferating cells. Estrogen drugs promote hyper-proliferation and this is one reason why these drugs may quadruple the incidence of breast cancer. [53]

Studies of breast cancer cells in culture indicate that tocotrienols have potent effects in inhibiting proliferation and inducing apoptosis (cancer cell death). These studies show that alpha tocopherol does not have this same benefit.

Estrogen sends messages to cells through what are known as estrogen receptors. Receptors are essentially "doors" on cells that allow entry of substances like estrogen. In the case of estrogen, the "door" is very big, and it will also allow molecules that resemble estrogen to enter as well. This is why fake estrogens and estrogen blockers can provoke cells to react. If the receptor was very small or very particular, it wouldn't allow the fakes in.

I3C does more than just turn strong estrogen to weak estrogen. 16-alpha-hydroxyestrone (16OHE) and 2-hydroxyestrone (2OHE) are metabolites of estrogen in addition to estriol and estradiol. 2OHE is biologically inactive, while 16OHE is biologically active-i.e., like estradiol, it can send those "grow" signals. In breast cancer, the bad 16OHE is elevated, and the good 2OHE is decreased. Interestingly, cancer-causing chemicals change the metabolism of estrogen so that 16OHE is elevated. Studies show that people who take I3C not only have beneficial increases in estriol, they also have beneficial increases in 2OHE.

I3C Stops Cancer Cells from Growing

I3C has other modes of action similar to tamoxifen. I3C also interrupts the cell cycle. In studies from the University of California mentioned above, I3C inhibited the growth of estrogen-receptor-positive breast cancer cells by 90% compared to tamoxifen's 60% by stopping the cell cycle. Adding tamoxifen to I3C gave a 5% boost (95% inhibition). In estrogen-receptor-negative cells, I3C stopped the synthesis of DNA for new cells by about 50% whereas tamoxifen had no significant effect. I3C also restores p21 and other proteins that act as checkpoints during the synthesis of a new cell. Tamoxifen has no effect on p21. Restoration of these growth regulators is extremely important. Tumor suppressor p53, for example, works through the p21 that I3C restores. I3C also inhibits cancers caused by other types of chemicals. If animals are fed I3C before exposure to cancer-causing chemicals, DNA damage and cancer is virtually eliminated. A study on rodents shows that damaged DNA in breast cells is reduced 91% by I3C. Similar results happen in the liver. And in a study from New York University Medical Center, female smokers taking 400 mg of I3C significantly reduced their levels of a major lung carcinogen. Cigarette chemicals are known to adversely affect estrogen metabolism.

The best and most comprehensive scientific evidence so far stands behind phytochemicals such as I3C. I3C beat out more than 80 other substances, including tamoxifen, for anticancer potential in one assay. Recently, researchers at the Hoechst Marrion Roussel drug company staked their claim to dozens of indole-3 look-alikes. They claim that the indoles, which down-regulate estrogen receptors, can be used to treat and prevent cancer and autoimmune diseases such as multiple sclerosis, arthritis, and lupus.

I3C Summary

A summary of recent studies shows that this vegetable extract (indole 3 carbinol) can

• Increase the conversion of estradiol to the safer estriol by 50% in 12 healthy people in just 1 week.
• Prevent the formation of the carcinogenic estrogen metabolite 16-alpha-hydroxyestrone in 2 months in 17 men and women.
• Stop human cancer cells from growing (54 to 61%) and provoke the cells to self-destruct (apoptosis).
• Inhibit MCF7 human breast cancer cells from growing by as much as 90% in culture.
• Inhibit an estrogen metabolite (16-alpha- hydroxyestrone) that prompts breast cancer cells to grow.
• Compete with dioxin for the Ah receptor to help keep dioxin out of cells. In breast cancer cells with I3C and dioxin at the same time, dioxin's adverse effects were reduced 90% by I3C.
• Prevent chemically induced breast cancer in rodents by 70 to 96%. Prevent other types of cancer, including aflatoxin-induced liver cancer, leukemia, and colon cancer.
• Inhibit free radicals, particularly those that cause the oxidation of fat.
• Inhibit the growth of estrogen-receptor-
  positive breast cancer cells by 90%, compared to tamoxifen's 60%, by stopping the cell cycle.
• Stop the synthesis of DNA for new cells by about 50% in estrogen-receptor-negative cells, whereas tamoxifen had no significant effect.
• Restore p21 and other proteins that act as checkpoints during the synthesis of a new cancer cell. Tamoxifen has no effect on p21.
• Virtually eliminate DNA damage and cancer if animals are fed it before exposure to cancer- causing chemicals.
• Reduce DNA damage in breast cells by 91%. Similar results happen in the liver.
• Reduce levels of a major carcinogen in female smokers.

Flavonoids

Genistein was tested with a number of other naturally occurring flavonoids and was found to inhibit cell proliferation in estrogen- receptor-positive breast cancer cells. This inhibition was reversed when excess competing estrogen was added. Interestingly, the other flavonoids inhibited cell proliferation even when high levels of estrogen were added suggesting that they work by a different mechanism than genistein. One of those flavonoids is quercetin. This suggests that taking supplemental quercetin might be useful in treating breast cancer. Quercetin is effective only in a water-soluble form, and it is difficult to find water-soluble quercetin

Melatonin

One of the most important supplements for the breast cancer patient is the hormone melatonin. High doses of the hormone should be taken at bedtime. Melatonin blocks estrogen receptors somewhat similarly to the drug tamoxifen without the long-term side effects of tamoxifen. Furthermore, when melatonin and tamoxifen are combined, synergistic benefits occur. Melatonin can be safely taken for an indefinite period of time. The suggested dose of melatonin for breast cancer patients is 3 to 50 mg at bedtime. Melatonin not only blocks estrogen-receptor sites on breast cancer cells, but directly inhibits breast cancer cell proliferation and boosts the production of immune components that kill metastasized cancer cells.

CoQ10

CoQ10 (Coenzyme Q10) has demonstrated promise in treating breast cancer. Although there are only a few studies, the safe nature of coQ10 coupled with this promising research suggests that breast cancer patients should take 100 mg 3 times a day. It is important to take coQ10 with some kind of oil such as fish or flax since dry powder coQ10 is not readily absorbed without it.