Cancer Adjuvant Therapy Protocol

Once activated, NK cells are dynamic in their search-and-destroy mission. Upon encountering an aberrant cell, stimulated NK cells attach to the membrane and inject cytoplasmic granules that quickly destroy or lyse the target. In less than 5 minutes, a worthy NK cell can kill a cancer cell and move on to the next objective. One NK cell can destroy up to 27 cancer cells in its lifetime, sometimes binding to and destroying two or more cancer cells at one time.

However, MGN-3 has an immune focus that extends beyond NK activation. It also increases levels of other immune-related cell populations (T-cells and B-cells) while increasing production of several cyto-kines, including interferon gamma, tumor necrosis factor, interleukin-12 (IL-12), and IL-2 (Ghoneum 1996). MGN-3 has been used effectively with IL-2, a protein that increases activated T cells. When MGN-3 is coupled with IL-2, the interleukin dosage can be reduced. This is extremely important because, unless the dosage is kept small, IL-2 can result in an assortment of hazardous side effects, negating any proposed advantage. Studies show that when MGN-3 and IL-2 are used in concert, they are often more effective immune system activators than either used alone (Ghoneum et al. 2000).

Dr. Ghoneum has published the results of 72 human trials, as well as test tube and animal studies in 7 different scientific and medical journals. The following statistics are excerpted from his research:

The Increase in Baseline NK-Cell Activity
after 2-Week Oral Ingestion of MGN-3
(45 mg/kg/day)
Breast Cancer Patients From ......145%-332%
Prostate Cancer Patients From ...174%-385%
Leukemia Patients From .............100%-240%
Multiple Myeloma Patients From 100%-537%

A 4-hour radioactive-chromium release assay is the standard test for measuring the activity of NK cells. During this test, white blood cells are incubated in vitro with a fixed number of chromium-labeled tumor cells. After 4 hours, the percentage of tumor cells that has been killed by the NK cell is determined; this percentage is used to describe NK cell activity.

According to Dr. Ghoneum, a healthy immune-competent individual will show NK activity in ranges from 60-75% at an effector to target ratio of 100:1; NK-cell activity in cancer patients typically ranges from 0-30%. It is unclear whether low NK-cell activity is a cause or a result of the cancer and the disease process. However, depreciated NK status is considered a risk factor for malignancy and metastasis, as well as a negative prognostic indicator regarding survival.

Debulking refers to any process such as chemotherapy, surgery, or radiation that reduces the cancerous volume. If the malignancy is advanced, MGN-3 cannot and should not replace debulking therapy. Dr. Ghoneum cautions that postponing debulking can be a significant hindrance to overcoming the malignancy. If the number of cancer cells already outnumber NK cells by too great a margin, the chances of the NK cells prevailing (even in their heightened state) are unlikely.

Ideally, a cancer patient begins MGN-3 therapy early into the disease process, while the tumor is still localized. Dr. Ghoneum speculates that in this case about 90% might (eventually) achieve complete remission. In advanced cancers with metastasis, Dr. Ghoneum says life span might increase from the expected 3-6 months to 1.5-2 years (McAllister 2001). Patients should consider supplementing with MGN-3 either during the debulking process or immediately after the procedure.

Dr. Ghoneum comments that conventional medicine has excellent antitumor therapies that can significantly reduce the number of cancer cells, but unfortunately it is difficult to achieve a 100% kill without killing the patient. Furthermore, it is not easy to detect small numbers of cancer cells, lying in wait to spring from latent to active states. Too often, conventional treatments render remissions that are at best short lived. Most cytotoxic therapies are themselves immunosuppressive, lowering the activity of anticancer effector cells.

Robust cancer cells that survived conventional therapy enjoy mounting a second attack against an impaired immune system. After its primary battle with cancer, the immune army is often weak and small in numbers and an easy target. All too often a cancer patient, pronounced in remission, suddenly presents with symptoms or laboratory tests that substantiate recurrence of the malignancy. Now the path becomes doubly treacherous, for conventional treatment (that worked earlier) may not be effective when repeated. Cancer cells have a killer intellect and use this wit to find a way around earlier effective drugs, a condition referred to as drug resistance. Dr. Ghoneum believes that introducing MGN-3 either very early in the disease process or after the tumor burden has been reduced, allows the body to destroy maverick cells that may have eluded traditional treatments. MGN-3, by resurrecting a weary immune system, dramatically improves prognosis.

Life Science reported that using MGN-3 (3 grams a day) often alleviates the side effects of cytotoxic therapies, improving quality of life (Jacoby et al. 2000). Also, administering MGN-3 in union with chemotherapy or radiation therapy helps white blood cells withstand the attack, allowing treatment to continue uninterrupted (Ghoneum 1998). (If white blood cell numbers plummet, therapy is suspended until the immune response is restored.)

A suggested MGN-3 dosage is 3 grams a day until all signs of cancer are gone. Continue with this dosage for an additional 2-3 months, reducing to 1 gram a day thereafter. Dr. Ghoneum believes many healthy individuals do well on a preventive dose of one-half gram a day; if the person is considered at high risk for cancer, the dosage should be increased to 1 gram a day.

Modified Citrus Pectin (MCP)--retards cancer growth and metastasis
Modified citrus pectin (MCP), also known as fractionated pectin, is a complex polysaccharide obtained from the peel and pulp of citrus fruits. Through pH and temperature modifications, the pectin is broken down into shorter, nonbranched, galactose-rich, carbohydrate chains. The shorter chains dissolve more readily in water, making them better absorbed than ordinary, long-chain pectin. The short polysaccharide units afford MCP its ability to access and bind tightly to galactose-binding lectins (galectins) on the surface of certain types of cancers. By binding to lectins, MCP is able to powerfully address the threat of metastasis (Strum et al. 1999).

In order for metastasis to occur, cancerous cells must first bind or clump together; galectin is thought responsible for much of cancer's metastatic potential by providing the binding site (Raz et al. 1987; Strum et al. 1999). MCP appears small enough to access and bind tightly with galectins, inhibiting (or blocking) aggregation of tumor cells and adhesion to surrounding tissue (Kidd 1996). Deprived of the capacity to adhere, cancer cells fail to metastasize.

The International Conference on Diet and Prevention of Cancer (Finland) announced that men with prostate cancer who took 15 grams of MCP a day had a slowdown in the doubling time of their PSA levels. (Lengthening of doubling time represents a decrease in the rate of cancer growth.) Interestingly, rats injected with prostate adenocarcinoma and given MCP (in drinking water) showed a significant reduction in metastasis (compared to control animals), although the primary tumor was unaffected. According to Dr. Kenneth Pienta (leader of the Michigan Cancer Foundation), MCP may be the first oral method of preventing spontaneous prostate cancer metastasis (Pienta et al. 1995).

As with prostate adenocarcinoma, research shows that metastasis of breast cancer cell lines requires aggregation and adhesion of the cancerous cells to tissue endothelium in order for it to invade neighboring structures (Glinsky et al. 2000). To test the anti-adhesive properties of MCP, researchers evaluated (in an in vitro model) breast carcinoma cell lines MCF-7 and T-47D. The study concluded that MCP countered the adhesion of malignant cells to blood vessel endothelia and subsequently inhibited metastasis (Naik et al. 1995).

One of the better models for studying metastasis is the highly metastatic mouse B16-F1 melanoma cell line. The Cancer Metastasis Program showed that MCP decreased metastasis of melanoma to the lung by more than 90% in laboratory animals (Platt et al. 1992).

Because MCP is a soluble fiber, no pattern of adverse reaction has been recorded in the scientific literature, apart from a self-limiting loose stool at high doses. MCP dosages are usually expressed in grams, with a typical adult dose ranging from 6-30 grams divided throughout the day. MCP's apparent safety, proven antimetastatic action, and the lack of proven therapies against metastasis appear to justify its inclusion in a comprehensive orthomolecular anticancer regimen (Kidd 1996). Pecta-Sol is the brand name of the original modified citrus pectin (MCA). (The dosage for Pecta-Sol is about 15 grams a day.)

N-acetyl-cysteine (NAC)--is an anticarcinogenic and antimutagenic agent; it inhibits IL-6 as well as invasion and metastasis of malignant cells
N-acetyl-cysteine (NAC) is the acetylated precursor of the amino acids L-cysteine and reduced glutathione. Historically, it is used as a mucolytic agent in respiratory illnesses as well as an antidote for acetaminophen hepatotoxicity, but more recently its credits have grown. Animal and human studies have shown it to be a powerful antioxidant and a potential therapeutic agent in the treatment of cancer.

The biological value of NAC is attributed to it sulfhydryl group, while its acetyl-substituted amino group offers protection against oxidative and metabolic processes (Bonanomi et al. 1980; Sjodin et al. 1989). In vitro studies showed NAC to be directly antimutagenic and anticarcinogenic; in vivo, NAC inhibited mutagenicity of a number of carcinogenic materials (De Flora et al. 1986, 1992).

NAC has both chemopreventive and therapeutic potential in malignancies arising in the lung, skin, breast, liver, head, and neck. Other researchers have noted NAC's effectiveness in inhibiting cell growth in melanoma and prostate cells and the proliferation of astrocytoma cell lines, a primary tumor in the brain (Albini et al. 1995; Arora-Kuruganti et al. 1999; Chiao et al. 2000). Neovascularization (new blood vessel growth) is crucial for tumor mass expansion and metastasis. NAC inhibited invasion and metastasis of malignant cells by up to 80% by preventing angiogenesis (De Flora et al. 1996).

A number of cancers express IL-6 and other potentially dangerous cytokines. NAC inhibited (in a dose-dependent manner) the synthesis of IL-6 by alveolar macrophage, hepatic production, TNF-alpha and bacterial lipopolysaccharides, a key component of the cell wall of gram-negative bacteria (Munoz et al. 1996; Gosset et al. 1999).

Peak plasma levels of NAC occur approximately 1 hour after an oral dose; 12 hours after dosing, it is undetectable. Despite a relatively low bioavailability (4-10%), research has shown NAC to be clinically effective (Borgstrom et al. 1986). A suggested NAC therapeutic dosage is usually in the range of 600 mg per day.

Resveratrol--influences cancer at initiation, promotion, and progression stages
The University of Illinois at Chicago (UIC) is home to the broadest-based chemoprevention drug discovery program in the world. Researchers there have analyzed and tested more than 2500 natural products for cancer-preventing properties since 1991. In 1997, a team led by pharmacy professor John Pezzuto announced that a substance in red wine, which was later named resveratrol, inhibited the onset and progression of cancer in mice.

UIC reported that resveratrol is one of a group of compounds (called phytoalexins) that are produced in plants during times of environmental stress, such as adverse weather or insect, animal, or pathogenic attack. Resveratrol has been identified in more than 70 species of plants, including mulberries and peanuts, but the skins of red grapes are a particularly rich source (Jang et al. 1999). According to Pezzuto, "Of all the plants we've tested for cancer chemopreventive activity and the compounds we've seen, this one [resveratrol] has the greatest promise" (Pezzuto 1997).

Pezzuto and colleagues were able to show that resveratrol was effective during all three phases of the cancer process: initiation, promotion, and progression. For example, resveratrol displayed antimutagenic and antioxidant activity, providing greater protection against DNA damage than vitamins C, E, or beta-carotene. UIC researchers showed that resveratrol restored glutathione levels, considered by some the most essential of antioxidants (Jang et al. 1999). It increased levels of a Phase II detoxifying enzyme (quinone reductase), an enzyme responsible for metabolically disassembling carcinogens. All three physiological effects are indicative of resveratrol preventing cancer at initiation, the often-irreversible first stage of the cancer process.

Resveratrol inhibited the activity of cyclooxygenase-2 (COX-2), reducing the inflammatory response in epithelial cells (Subbaramaiah et al. 1999). Upregulation of COX-2 is associated with the physical manifestations of various human cancers, as well as inflammatory disorders. Since inflammation is closely linked to tumor promotion, substances with potent anti-inflammatory activities are thought to exert chemopreventive effects, particularly in the promotion stage of the disease.

Resveratrol prompted differentiation of human promyelocytic leukemia cells, indicating that it depressed the progression phase of cancer; the development of preneoplastic lesions in mouse mammary glands were likewise inhibited. Trials to determine the effects of resveratrol on the three stages of cancer were completed without toxicity to blood-forming cells.

The following studies illustrate the many pathways resveratrol employs to inhibit cancer:

Italian researchers recently determined that resveratrol exhibited a protective role against colon carcinogenesis, with the defense attributed to changes occurring in Bax protein, which encourages apoptosis, and p21 expression (Tessitore et al. 2000). Reduced Bax activity is associated with metastasis, dysfunction of apoptotic mechanisms, and resistance to cytotoxic therapy (Bosanquet et al. 2002). p21 is able to arrest the cell cycle at the G1 phase by inhibiting DNA replication (Aaltomaa et al. 1999). Suppressing the growth cycle allows for a critical phase in cellular development referred to as differentiation, that is, an atypical cell becomes more typical.
Resveratrol appears a promising anticancer agent for both hormone-dependent and hormone-independent breast cancers. At high concentrations, resveratrol caused suppression of cell growth in three breast cancer cell lines: ER-positive KPL-1 and MCF-7 and ER-negative MKL-F. Growth inhibition was credited in part to upregulation of Bax protein and activation of caspase-3 (a key mediator of apoptosis in mammalian cells). Resveratrol was also able to lessen the growth stimulatory effects of linoleic acid, a fatty acid frequently overconsumed in Western diets (Nakagawa et al. 2001).
Resveratrol significantly reduced tumor volume (42%), tumor weight (44%), and metastasis (56%) in mice with highly metastatic Lewis lung carcinoma. Researchers noted resveratrol's ability to inhibit angiogenesis and reduce oxidative stress (Kimura et al. 2001; Kozuki et al. 2001).
Of special interest is the recent finding that different wine polyphenols (catechin, epicatechin, quercetin, and resveratrol) may be effective against prostate cancer. Prostate cancer cell lines (LNCaP and DU145) produce high concentrations of nitric oxide; PC3 produces low concentrations. Researchers propose that the antiproliferative effects of polyphenols are due to their ability to adjust nitric oxide production (Kampa et al. 2000). Grape extract, a rich source of resveratrol, inhibited prostate cancer growth up to 98% in a dose- and time-dependent manner (Agarwal et al. 2000b).
Resveratrol appears to be promising in the control of acute monocytic leukemia (Tsan et al. 2000). The journal Blood reported that resveratrol induced apoptotic cell death in HL60 human leukemia cells (Clement et al. 1998) and stopped growth of lymphocytic leukemia cells during the S-Phase of the growth cycle (the time of DNA replication) (Bernhard et al. 2000).
Oncology Research Laboratory (Detroit) showed that resveratrol inhibits NF-kB, thus inhibiting cell proliferation and cytokine production (Gao et al. 2001). The fact that some antioxidants are known to be strong inhibitors of NF-kB appears another of the pathways antioxidants employ to protect against cancer. Researchers found the inhibition of cytokine production by resveratrol irreversible.
If using pure resveratrol, the suggested dosage is 7-50 mg a day. Beware of diluted supplements that provide very little actual resveratrol. At the time of this writing, there were only a few sources of pure high-potency resveratrol that are just coming onto the dietary supplement marketplace.

Selenium--is protective against many types of cancers, promotes apoptosis, is a powerful antioxidant, and improves quality of life during aggressive cancer therapies
According to P.D. Whanger (professor of agricultural chemistry), nearly 200 animal studies have been conducted to evaluate the effects of supernutritional levels of selenium on experimental carcinogenesis using chemical, viral, and transplantable tumor models. Two thirds of the studies found that high levels of selenium reduced the development of tumors at least moderately (14-35% compared to controls) and, in most cases, significantly (by more than 35%) (Whanger 1998).

Selenium levels, judged adequate because they exceed deficiency states, appear misleading. To explore the impact of selenium on basal cell carcinoma, researchers enrolled 1312 subjects (18-80 years of age, 75% of whom were men) in a study to determine the impact of selenium supplementation on basal cell carcinoma (Clark et al. 1996).

Within 6-9 months, the group receiving 200 mcg a day of selenium realized about a 67% increase in plasma selenium levels. The group not being supplemented, although judged "normal" in regard to plasma selenium levels, experienced twice the rate of cancer as those receiving selenium. Researchers concluded that greater amounts of dietary selenium are needed to prevent cancer than the amount recommended by the FDA.

Although the study failed to show the effectiveness of selenium in altering the course of either basal or squamous cell carcinoma, selenium impacted the incidence of other types of malignancies with amazing success (Clark et al. 1996). The overall reduction in cancer incidence was 37% in the selenium-supplemented group; a 50% reduction in cancer mortality was observed over a 10-year period.

The following are the site-specific reductions in cancer incidence observed in the study: colon-rectal cancers (58%), lung cancer (46%), and prostate cancer (63%). A selenium deficiency appears to increase the risk of prostate cancer fourfold to fivefold. It was determined that, as the male population ages, selenium levels decrease, paralleling an increase in prostate cancer (Brooks et al. 2001).

Data is compelling regarding the usefulness of selenium as a cancer protective:

The Journal of Nutrition reported that selenium-enriched broccoli is protective against chemically induced mammary and colon cancer in rats (Davis et al. 2002). Note: While selenium is contributing to the lower incidence of malignancy, the anticancer affects of broccoli should also be factored into the defense. Please read the section What Should the Cancer Patient Eat (appearing in this protocol) for valuable information regarding dietary factors affecting patient outcome.
In a study published in the Journal of the National Cancer Institute, the relationship between serum levels of selenium and the development of upper digestive tract cancer was explored (Mark et al, 2000). The relative risk of esophageal cancer was 0.56 in individuals in the highest quartile of selenium level compared with those in the lowest quartile. The corresponding relative risk of gastric cardia cancer was 0.47. Based on the data, the researchers calculate that 26.4% of esophageal and gastric cardia cancers are attributable to low selenium levels.
A study conducted in China showed that adding selenium to salt resulted in a significant reduction in the incidence of cancer (Whanger 1998).
Researchers at Charles R. Drew University of Medicine and Science observed a significant increase in apoptosis and a decrease in DNA synthesis in MCF-7 and SKBR-3 breast cancers with selenium supplementation. The selenium benefit was just as impressive in cancers of the lung (RH2), small intestine (HCF8), colon (Caco-2), and liver (HepG2). Prostate cancers (PC-3 and LNCaP) as well as colon cancer (T-84), although initially less affected by supplementation, became responsive when selenium was coadministered with Adriamycin or Taxol (Vadgama et al. 2000). This study suggests that selenium (a respected antioxidant) potentiates the chemotherapeutic index rather than degrading it, as some feared. Reports from Germany indicate that selenium supplementation in patients undergoing radiation therapy for rectal cancer improved quality of life and reduced the appearance of secondary cancers (Hehr et al. 1997).
It appears that selenium acts as an immunologic response modifier, normalizing every component of the immune system (Life Extension Report 1995).
A particularly worthy form of selenium is Se-methylselenocysteine, currently available and attracting positive attention. This is the form of selenium found naturally in plants such as broccoli and garlic. A suggested selenium dosage (as a preventive) is 200 mcg a day. The optimal dose for the cancer patient is unknown at this time, but suggestions have ranged from 200-400 mcg a day. Depending upon the selenium content of the soil, foods considered to be good sources of selenium include Brazil nuts, grains, onions, tomatoes, broccoli, chicken, eggs, garlic, liver, seafood, and wheat germ. Americans typically get from 60-100 mcg of selenium a day from dietary sources.

Silibinin (from milk thistle)--has antioxidant activity, increases sensitivity to chemotherapy while reducing its side effects, assists in arresting the growth of cancer, promotes differentiation, inhibits COX-2 enzyme, has a regulatory mentality, and suppresses NF-kB
Fourteen years ago, the Life Extension Foundation introduced silymarin, a hepatoprotective German drug, to members. The major active constituent of silymarin is silibinin, a long-recognized antioxidant with more recently ascribed anticarcinogenic traits. Silibinin inhibits various cancer cell lines, but an additional advantage was credited to the bioflavonoid when it was found that silibinin acts synergistically with cisplatin and doxorubicin, common chemotherapeutic drugs, improving their efficiency. By arresting tumor cell division at a strategic stage, silibinin appears to make tumor cells more sensitive to chemotherapy. Also, the harsh effects associated with cytotoxic chemicals are less damaging when silibinin is utilized (Bokemeyer et al. 1996).

Milk thistle is described as an adaptogenic, or smart herb. For example, it encourages new cell growth where repair is needed but arrests cell division in tumor tissue; it increases the activity of certain enzymes but inhibits others. Milk thistle also joins a growing list of natural products identified as COX-2 inhibitors (Zhao et al. 1999). Note: Turn to Cyclooxygenase (COX-2) Inhibitors (Naturally Occurring) appearing in this protocol for other nutraceuticals capable of inhibiting the COX-2 enzyme. Also, consult Cyclooxygenase Inhibitors in the protocol entitled Cancer Treatment: The Critical Factors to learn more about the COX-2-cancer connection.

Silibinin arrests cell growth in the early phase of the cycle known as G1, a period of growth before DNA replication. Silibinin possesses another trait that discourages cell growth, that is, the ability to inhibit various kinase enzymes (those playing a pivotal role in regulatory mechanisms). These traits permit a critical stage in cellular development referred to as differentiation. Differentiated cells abandon their primitive façade and assume the physical likeness and behavioral patterns of healthy cells. In fact, silibinin transformed a significant number of malignant prostate cells to more normal cells, while simultaneously decreasing PSA levels (Zi et al. 1999).

The European Journal of Cancer reported the value of silibinin in drug-resistant breast and ovarian cancer lines. It appears silibinin, a flavonoid, binds to Type II estrogen binding sites, an action that turns off the proliferative effects of the cell (Scambia et al. 1996). In addition, silymarin inhibited the secretion of VEGF (an angiogenic factor) by malignant cells, thwarting the formation of cancer's vascular network (Jiang et al. 2000).

The University of California (Berkeley) announced that silymarin potently suppressed NF-kB, but TNF-alpha-induced NF-kB was not affected, demonstrating a pathway-dependent inhibition by silymarin. It appears the inhibitory effect of silymarin on NF-kB activation is associated with its liver-protecting properties. Suppression of NF-kB, a key regulator in inflammatory and immune reactions, significantly advances the anticarcinogenic status of silymarin (Saliou et al. 1998).

Silymarin-silibinin is remarkable medicine for the liver. Numerous studies show that milk thistle is effective in treating virtually every type of liver disease, including cirrhosis and alcohol or chemical-induced liver damage. So worthy is the herb in protecting against life-threatening toxins that individuals poisoned by the Amanita mushroom survived the experience when silibinin was utilized (Carducci et al. 1996). A healthy liver is essential to detoxification, a process key to restoring health to cancer patients.

Standardized milk thistle extract usually consists of 35% silibinin, whereas the silymarin concentrate used in Europe contains a minimum of 80% silibinin. The Life Extension Foundation recommends the highly beneficial 80% silibinin extract. A suggested therapeutic dosage of Silibinin Plus is up to 6 capsules daily (1950 mg a day). For protection, use about 1-2 capsules (325-650 mg a day).

Soy--is protective against certain malignancies, appears to be an alternative to signal transduction-inhibiting drugs, and inhibits angiogenesis, cell proliferation, and metastasis

Legumes, including the soybean, contain bioactive compounds that researchers have been able to isolate and study in the laboratory. These compounds are classified broadly as phytoestrogens. It is misleading to call them estrogens, and some researchers have objected. Phytoestrogens are nonsteroidal and can actually inhibit steroids such as aromatase. Most have little or no estrogenic activity. When they do have such activity, it is usually beneficial and specific to a certain tissue. For example, some soy isoflavones (a type of phytoestrogen) benefit bone but do not affect the kidney. In drug lingo, this is called a selective estrogen receptor modulator (SERM). A compound in soy, genistein, is a natural SERM. Tamoxifen and Raloxifen are chemical SERMs (Setchell et al. 1999).

The latest science available suggests that the reason that different estrogens have different effects on different tissues is because there is more than one type of estrogen receptor. So far, three variations on the estrogen receptor have been found: alpha and two betas. They share a same basic estrogen structure but with a slight variation. The variation is critical, for researchers believe that the estrogen beta receptor (ERb) may suppress the action of the alpha receptor (ERa)--at least in cancer cells (Maruyama et al. 2001; Saji et al. 2002; Speirs et al. 2002). And the strong, growth-promoting estrogens such as estradiol, activate ERa. Phytoestrogens preferentially activate the beta, or repressive, receptor (Barkhem et al. 1998). For this reason, phytoestrogens have been characterized as good estrogens, and whatever estrogenic effect they themselves have (which is estimated to be 1000-10,000 times weaker than estradiol, if it exists at all) may be nullified by their inhibition of estrogen synthesis and repression of the receptor doorway that allows estradiol into the cell (Shao et al. 2000).

In normal tissue, the two estrogen receptors apparently work together to control both the amount and the use of estrogen in the body. It has been demonstrated that some types of cancer cells lose one type of estrogen receptor, leaving the control mechanism inoperable (Iwao et al. 2000; Sampath et al. 2001). This phenomenon has been demonstrated in prostate cancer. Some types of prostate cancers have lost their alpha receptors and some have lost beta. This is why some will respond to estrogen and stop growing and others will stop growing when an antiestrogen, such as genistein or Tamoxifen, is added.

The loss or gain of receptors occurs because of methylation abnormalities that occur in DNA (Lau et al. 2000). DNA methylation abnormalities are caused by three known things: poor diet (i.e., a diet lacking in methylation factors including folate, vitamins B6 and B12), chemicals, and age.

Phytoestrogens include many diverse plant compounds, including resveratrol from grapes, curcumin from roots, and polyphenols from tea leaves. It is a very broad category that is further broken down into dozens of classifications such as flavonoids, flavones, and so forth. The anticancer effects of phytoestrogens are the subject of hundreds of scientific studies.

Soy Isoflavones
Soy contains phytoestrogens known as isoflavones. Daidzein, coumestrol, and genistein are the most studied. Isoflavone supplements contain a mixture of many different types of these compounds. Researchers have barely scratched the surface of understanding what they can do. Interest in their anticancer potential stems from the big difference in the lower occurrence of hormone-related cancers in Asians who eat a lot of soy and Westerners who do not. It is doubtful that the low rates of breast, prostate, and other hormonally related cancers are due solely to soy products, but studies show that compounds isolated from soy do have significant anticancer effects.

Soy for Prostate Cancer
The most dangerous aspect of prostate cancer is metastasis, or spreading, to other areas. Prostate cancer can be controlled if it can be limited to the prostate gland. Unfortunately, many men with prostate cancer have undetected metastases. The name of the game with prostate cancer is to detect it early and stop metastasis.

Researchers at Wayne State University have published a groundbreaking study that demonstrates that genistein has powerful and specific effects against the spread of prostate cancer. They added genistein in varying amounts to prostate cancer cells growing in a test tube. They then performed a sophisticated test to determine what effects the soy derivative had on the activation of genes. This is important because genes make proteins, and proteins can either enable or stop a cancer. They found that genistein significantly activated 832 genes in prostate cancer cells, 13 of which are related to metastasis.

Among the proteins downregulated by genistein's effects on genes were ones that make proteins that dissolve surrounding tissue to enable metastasis, ones that enable a cancer cell to invade surrounding tissue, and ones that create new blood vessels to feed the tumor. The effects of genistein were very powerful, with some genes being deactivated by more than tenfold. Although they only reported on genes having to do with metastasis, the authors noted that genistein also affected genes playing important roles in stopping the cell cycle, differentiation (having cells grow up and quit dividing), apoptosis, and cell signaling (talk between cancer cells) (Li et al. 2002).

Other studies by the same researchers show that genistein stops prostate tumor growth and causes the cells to die (Davis et al. 1999). Genistein has "potent antiproliferative effects" against human prostate cells, according to researchers at M.D. Anderson (Shen et al. 2000). It stops metastasis (Schleicher et al. 1999). And in cancer cells growing in a test tube, the more the genistein, the greater the effect.

Genistein is one component of soy. Other studies show that soy itself has powerful effects in the prevention and eradication of prostate cancer. No negative effects have been demonstrated. It appears that different components of soy have different effects against prostate cancer cells. One very interesting study shows that genistein blocks an enzyme that destroys an anticancer vitamin D metabolite in cancer cells (Farhan et al. 2002).

Prostate cancer is a hormone-related cancer. In perhaps the most comprehensive study ever, researchers at Harvard and the University of Hawaii fed mice three different soy products: soy protein without isoflavones, soy phytochemical concentrate (a combination of genistein, daidzein, glycitein, and other compounds), and genistein. They discovered that all three have a positive effect on hormones as they relate to the growth of prostate cancer. The cancer cells they used are androgen-sensitive. The androgen receptor, which correlates with tumor weight, was reduced 42% by soy protein. Genistein reduced serum dihydrotes-tosterone, a form of testosterone associated with hyperplasia and cancer, and caused a 57% reduction in tumor growth. Soy phytochemical concentrate inhibited the overall growth of prostate cancer 70%. Cell death was induced, and angiogenesis was significantly inhibited. Soy phytochemical concentrate also stopped metastases to lymph nodes and lung (Zhou et al. 2002).

This comprehensive study is only one of many studies on soy and prostate cancer. Researchers at the University of Alabama recently reported that healthy, normal rodents fed genistein for 2 weeks at a dietary level had significant reductions in androgen and the two estrogen receptors (Fritz et al. 2002). Minimizing the number of hormone receptors reduces levels of cell growth-promoting hormones in the prostate gland. Korean researchers recently compared the levels of phytoestrogens in 25 men with and without benign prostatic hyperplasia (prostate enlargement), a noncancerous overgrowth of prostate cells. Genistein was the only agent that emerged as significant. The genistein levels in men with prostate enlargement were significantly lower than in those without (Hong et al. 2002). A study from AntiCancer in San Diego shows that adding genistein to prostate tissue taken from men with prostate enlargement will stop the growth. It also stops the growth of prostate cancer in tissue taken from men with prostate cancer (Geller et al. 1998).

Cancer Adjuvant Therapy Pg (1) (2) (3) (4) (5) (6) (7)

These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease