~Cancer Adjuvant Therapy, Part 6


Soy and Other Types of Cancer

  • Glioma
  • Bladder Cancer
  • Stomach Cancer
  • Melanoma
  • Lung Cancer
  • Colon Cancer
  • Thyroid Cancer
  • Leukemia

Soy has powerful anticancer effects that do not involve hormones. Genistein inhibits a chemical reaction used by many different types of cancer cells to multiply and spread. Compounds that can do this are called tyrosine kinase (TK) inhibitors. Dozens of studies in different types of cancer cells show that genistein is a powerful and effective TK inhibitor.

Glioma. Glioma cancer cells have very high TK activity, which correlates with cancer growth. Several in vitro studies show that genistein inhibits the growth of glioma (Baltuch et al. 1996; Tu et al. 2000; Khoshyomn et al. 2002). Genistein also enhances the effectiveness of the chemotherapeutic drugs carmustine and camptothecin with a 40% decrease in growth and a 50% increased killing effect in some cells (Ciesielski et al. 1999; Khoshyomn et al. 2002). The amount of genistein needed to enhance the effectiveness of carmustine is not high.

Bladder Cancer. Genistein's ability to inhibit TK may be of great benefit in keeping bladder cancer localized. In Asia, the incidence of invasive bladder cancer is much lower than in the United States, leading some researchers to investigate the effects of soy. Invasive bladder cancers have high levels of a protein known as epidermal growth factor receptor (EGFR), which enables the cancer to invade muscle. EGFR is activated by TK and can be reversed by genistein (Theodorescu et al. 1998).

The effects of genistein, soy protein isolate, and soy phytochemical concentrate on human bladder cancer cells and bladder cancer were studied in mice. The three soy products reduced tumor volume 40%, 37%, and 48%, respectively. They blocked tumor blood vessel formation and induced tumor cell death, stopping the cells from growing at the G2-M part of the cell cycle (Zhou et al. 1998).

A mixture of isoflavones work better than a single soy compound for bladder cancer. In a study on seven different cell lines, genistein plus isoflavones inhibited tumor growth and induced cell death at levels obtainable through the diet or soy supplements. Both genistein and combined isoflavones exhibited a significant tumor suppressor effect in vivo. These results justify the potential use of soybean isolateas a practical chemoprevention approach for patients with urinary tract cancer (Su et al. 2000).

Stomach Cancer. The effects of soy products on 10 different types of human gastrointestinal cancer cells found that genistein and biochanin A (a genistein precursor) strongly inhibited proliferation of stomach, colon, and esophageal cancers (Yanagihara et al. 1993). Data from a study involving over 30,000 people was analyzed and it was found that people who eat the most soy products reduced their risk of stomach cancer by half compared to those who eat the least (Nagata et al. 1998).

Melanoma. Studies on the effects of genistein on human melanoma cancer cells showed that genistein is a powerful inhibitor of the growth of this cancer and that it stops the cell cycle as effectively as the chemotherapeutic drugs adriamycin and etoposide (Darbon et al. 2000).

Studying melanoma in mice revealed that genistein reduces the blood supply to lung tumors and has an additive effect with the drug cyclophosphamide. In laboratory rodents, genistein can reduce the growth of tumors by half through supplements and/or diet (Record et al. 1997).

Lung Cancer. Genistein has several actions against small cell and non-small cell lung tumors. In a study in which Lewis lung cancer was transplanted into mice, genistein reduced the tumor colonies by half, and genistein plus cyclophosphamide reduced them by 90% (Wietrzyk et al. 2001). Several studies show that genistein stops lung cancer cells from growing and induces cell death (Tallett et al. 1996; Fujimoto et al. 2002; Wietrzyk et al. 2000). Genistein inhibits enzymes that help lung cancer cells to proliferate and spread (Leyton et al. 2001). Genistein up-regulates tumor suppressor genes p53 and p21 (Lian et al. 1999). Genistein reverses the multidrug resistance-associated protein, a protein that makes lung cancer cells resistant to daunorubicin, doxorubicin, etoposide, and vinblastine (Versantvoort et al. 1994; Berger et al. 1997).

Researchers in Japan analyzed information from 333 people with lung cancer. They found that eating tofu every day reduced the risk of lung cancer 45% in men and 86% in women (Wakai et al. 1999).

Colon Cancer. Soy has anticancer effects against cells that line the digestive tract. For this reason, it may have beneficial effects against different types of digestive tract cancers. Researchers looking at how three different types of human colon cancer cells react to soy confirmed that colon cancer is susceptible to soy's anticancer effects (Zhu et al. 2002). Some colon cancers may be estrogen dependent. Estradiol activates four kinase enzymes in colon cancer cells, two of which are tyrosine dependent and therefore potentially susceptible to genistein. Genistein blocks at least one of these enzymes and retards cell growth (Di Domenico et al. 1996). Genistein also suppresses the growth of nonestrogen-dependent colon cancer cells, which also respond to treatment with tamoxifen (Arai et al. 2000).

In a study that investigated how tamoxifen, genistein, and estradiol affect intestinal cells, genistein and tamoxifen emerged as the strongest inhibitors of cell proliferation, inhibiting TK and inducing the death of cancer cells (Booth et al. 1999). Genistein reverses resistance to doxorubicin and other chemotherapeutic drugs in at least one type of colon cancer by a "novel drug resistance pathway" (Rabindran et al. 1995). However, a study in mice showed that soy isoflavones may not counteract a bad diet. Mice fed a Western high fat, low fiber, and low calcium diet developed colon cancer despite isoflavones in their food (Sorensen et al. 1998). Soy could not reverse colon cancer (whereas rye lignans could) in mice on high fat diets (Davies et al. 1999).

Thyroid Cancer. Soy may have beneficial effects against thyroid cancer. Six hundred and eight cases of thyroid cancer, found that people who consume soy compounds, genistein and daidzein, in their diet reduced their risk of this cancer by one-third. However, adding soy flour or protein to a Western diet was not effective (Horn-Ross et al. 2002).

Leukemia. A few studies have been done on human leukemia cells treated with genistein. Of nine compounds tested, genistein showed the strongest inhibitory effects against human promyelocytic leukemia (HL-60) cells. All nine compounds are found in miso (Hirota et al. 2000). In human leukemia cells resistant to chemotherapy, genistein was able to reverse the drug resistance almost completely (Nagasawa et al. 1996). The anti-proliferative effect of genistein against human leukemia was significantly augmented by vitamin D analogs (Siwinska et al. 2001).

Free-Radical Scavenging Effects

The antioxidant effects of soy were the focus of much of the early research on how soy prevents cancer. The powerful free-radical scavenging effects of soy compounds and how they impact cancer continue to emerge.

Soy has an additive effect with vitamin E; it lowers rather than elevates estrogen levels in women and androgen levels in men (Jenkins et al. 2000). Damage to DNA caused by certain types of free radicals is strongly inhibited by genistein and other soy compounds (Breinholt et al. 1999; Davis et al. 2001). This helps prevent cancer. Dietary amounts significantly lower free-radical damage (Davis et al. 2001; Exner et al. 2001).

In addition to blocking free-radical damage, soy phytoestrogens also block inflammation, a contributor to cancer growth, notably in the colon (Davis et al. 2001; Zheng et al. 2002).

The effects of genistein against the activation of EGFR by free radicals were demonstrated. In this study, genistein reversed the free-radical activation of EGFR in normal cells (Chen et al. 2001). The benefits of genistein against oxidative stress are evident from a study on brain cells exposed to hydrogen peroxide. Free radicals generated by this oxidant degrade phospholipids and activate enzymes, which are crucial for memory and other brain functions. Genistein, through its ability to inhibit a tyrosinekinase enzyme that sets off the reaction, rescues cells from damage (Servitja et al. 2000).

Soy Precautions and Dosage

While the data are persuasive regarding the chemoprotective effects of soy, many questions remain. Some nutritionally based oncologists do not permit soy in their patients' regime. Others believe that soy should be avoided by everyone and have launched massive public relations campaigns to discredit soy and discourage even moderate consumption by healthy people.

Breast cancer patients should avoid soy until their estrogen receptor status has been determined. Estrogen receptor alpha-positive breast cancer patients may benefit from genistein, while beta-receptor positive breast cancer patientsí tumors cells may proliferate faster in response to genistein. It has been suggested that patients avoid soy supplements 1 week prior to, during, and 1 week after radiation therapy, although new studies appearing in the Cancer Radiation Therapy protocol indicate a potential benefit to using soy isoflavones during radiation therapy.

Some people believe that soy is toxic to the thyroid gland, yet this may be a concern only in cases of iodine deficiency (Doerge et al. 2002). Some of the more credible arguments deal with soy-based infant formulas (Tuohy 2003).

There are a number of human clinical studies being conducted on the use of soy to both prevent and treat cancer (http://clinicaltrials.gov/ct/search?term=soy). When the findings of these studies are published, perhaps more definitive recommendations can be made about soy supplements. Based on the information available to us as of this writing, those concerned about cancer may consider these guidelines: a suggested dosage is five 700-mg capsules 4 times a day of a soy extract providing a minimum of 40% isoflavones. For prevention purposes, as little as 135 mg of a 40% soy isoflavone extract once a day may be adequate.

Theanine--increases efficacy of chemotherapeutic drugs

Researchers speculate that drinking 1 cup of green tea favors a positive mental attitude and increases the efficacy of chemotherapy. However, components of green tea have been identified (caffeine, epigallocatechin gallate (EGCG), flavonoids, and theanine) that better explain the chemotherapeutic advantage beyond its soul-soothing effects (Sadzuka et al. 2000a).

Japanese researchers focused specifically on theanine and its influence on the anti-tumor activity of Adriamycin (doxorubicin). In vitro, theanine inhibited the outflow of Adriamycin (ADR) from cancerous cells, increasing concentrations within the cell by almost three-fold. An increase in ADR concentrations was not observed in normal tissues, suggesting theanine protects healthy organs, such as the heart and liver. (Sadzuka et al. 1996). Illustrative of the enhancing qualities of theanine, injecting ADR into ovarian sarcoma-bearing (M5076) mice did not inhibit tumor growth, whereas a combination of theanine and ADR reduced tumor weight 62% (Sugiyama et al. 1998).

When theanine was added to pirarubicin, intracellular concentrations of pirarubicin increased 1.3-fold and the overall therapeutic efficacy of the drug increased 1.7-fold (Sugiyama et al. 1999). Satisfying results were also found when theanine was used with Idarubicin (IDA), which is highly toxic to bone marrow and an anti-leukemia agent similar to doxorubicin. Risk factors permitted only about one-fourth of the standard IDA dose to be used in combination with theanine. However, theanine reduced toxicities and increased IDA anti-tumor activity, rendering the chemotherapeutic agent a possibility for the treatment of leukemia (Sadzuka et al. 2000b).

Part of theanine's anticancer effects can be attributed to mimicking glutamate, an amino acid that potentiates glutathione. Glutathione detoxifies chemotherapeutic agents, barricading chemicals from cells, and inhibiting tumor cell kill. Theanine is structurally similar to glutathione and crowds out glutamate transport into tumor cells. Cancer cells (in confusion) erringly take in theanine and theanine induces glutathione production. Glutathione (derived from theanine) does not detoxify like natural glutathione, and instead blocks the ability of cancer cells to neutralize cancer-killing agents. Deprived of glutathione, cancer cells cannot remove chemotherapeutic agents, and the tumor cell dies as a result of chemical poisoning (Sadzuka et al. 2001).

Administered with doxorubicin, the suggested dose of theanine is 500-1000 mg a day, although no human studies have been conducted with chemotherapy and theanine.

Thymus Extract--improves T-cell response and regulates the activity of cytokines

The thymus gland was at one time removed as an unnecessary appendage. It is an essential organ of the immune system, increasing stamina, energy, well-being, and the ability to ward off infections and cancer. Since 1965, when Burnet was awarded the Nobel Prize for demonstrating the endocrine function of the thymus gland, medical interest has focused on the thymus. It is now largely accepted that the thymus gland plays a central role in the mammalian immune system.

The immune system is made up of B-cells that protect against bacterial and viral infections and T-cells that guard against viral and fungal infections, as well as cancer. This powerful body of cells normally treats a developing cancer as foreign tissue, destroying aberrant cells before rapid multiplication occurs.

The effectiveness of T-cell mediated immunity depends upon the activity of T-lymphocytes (T-cells), which are programmed by proteins from the thymus gland. Immature (naÔve) T-4 cells do not function properly until programmed by thymic proteins. As new T-lymphocytes migrate from the bone marrow to the thymus, they are programmed to distinguish between self-tissue (the host) and nonself tissue (an invading pathogen).

The thymus gland, a lymphoid organ situated in the anterior superior mediastinum, reaches its maximum weight near puberty and then undergoes involution, or degenerative change, shrinking to about one-sixth of its original size. By the age of 40, the thymus gland is scarcely functional in many individuals; therefore, the essential thymus-provided protein is no longer available to program T-4 cells. More than 20 years ago, thymic protein A was isolated and purified from bovine thymus cells (by Dr. Terry Beardsley, an immunologist). Dr. Beardsley patented a technology to grow thymus cells in the laboratory and then purify a specific thymus protein (Thymic Protein A) that helps T-cells to mature with immune competency. The active ingredient in Thymic Protein A is the precise thymus protein that programs the T-4 lymphocytes to locate abnormal cells and then directs T-8 killer cells to destroy them.

Three types of cells emerge from the thymus: T-4 helper cells (master regulators), T-8 cytotoxic killer cells (guided by T-4 helper cells to attack and destroy invading cells), and T-8 suppressor cells. T-4 helper cells regulate many key functions, including the activity of IL-2 and interferon.

High dose thymosin, a humoral factor secreted by the thymus, in conjunction with intensive chemotherapy was administered to 21 patients with advanced lung cancer. Ordinarily, patients with late stage lung cancer live about 240 days; the median survival rate more than doubled (500 days) among patients receiving thymosin. Some of the thymosin-treated group were alive and disease-free 2 years after treatment (Chretien et al. 1979).

Blood tests to measure the immune response are extremely valuable when detailing either a preventive or a therapeutic program to fight cancer. While determining T-lymphocyte numbers is important, assessing their activity is even more crucial. It is possible for a person with a total count of 1000 T-4 cells to have only 50% of these cells activated by the thymus. It is important that the patient know the degree of immune impairment in order to structure a corrective program. Tests to evaluate the activity of the immune system are performed at the Immuno-Science Laboratory (Los Angeles), (310) 657-1077.

A suggested dosage for healthy individuals is 1 packet of BioPro Thymic Protein A daily or every other day. Cancer patients may wish to increase this amount. For example, HIV patients use 3 doses a day until blood tests remain normal for 3-6 months. For maintenance, reduce to 1 dose a day. Use the thymic protein under the tongue, retaining for 3 minutes to allow for maximum absorption. Typically, patients undergoing chemotherapy maintain acceptable white blood cell counts if Thymic Protein A accompanies treatment.

Continued . . .

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