General Information

The root of the legume Astragalus membranaceus (milk vetch or yellow vetch) is one of the most common tonic herbs in Chinese herbal medicine. Astragalus is a very large genus in North America there are nearly 400 Astragalus species, located mainly in the western United States. Some of these, such as the infamous loco-weed, are poisonous to livestock due to their high selenium content. Other species of Astragalus, like membranaceus, are nontoxic. The common food and cosmetic ingredient, gum...

References

Review The role of glutathione in the regulation of apoptosis. Eur J Clin Invest 1999 Mar 29(3) 238-45. 2 Voehringer DW. BCL-2 and glutathione Alterations in cellular redox state that regulate apoptosis sensitivity. Free Radic Biol Med 1999 Nov 27(9-10) 945-50. 3 Obrador E, Navarro J, Mompo J, et al. Regulation of tumour cell sensitivity to TNF-induced oxidative stress and cytotoxicity Role of glutathione. Biofactors 1998 8(1-2) 23-6. 4 Nakanishi Y, Kawasaki M, Bai F, et al....

Introduction To The Compounds

Of the hundreds of natural compounds known to be active against cancer (at least in vitro), this book focuses primarily on only 38. This is clearly a very small percentage. Narrowing the focus was necessary for several reasons. For one thing, few data are available for most of those known to be active. For another, many would not be safe for human consumption. For these and other reasons, a set of criteria was used to narrow the focus compounds were included that met most, if not all, of the...

Increased Plasma Membrane Fluidity

Polyunsaturated fatty acids can increase fluidity of the plasma membrane of tumor cells. Membrane fluidity is a measure of the ability of lipid molecules (and the proteins they sandwich) to move about fluidity thus affects a In plasma, the omega-6 to omega-3 ratio changed from 0.9 to 0.41. To give an idea of plasma concentrations, the total omega-3 fatty acid concentration changed from 390 to 1,200 jM. EPA plasma concentrations changed from 34 to 690jM and DHA plasma concentrations changed from...

Use of Immunotherapy in Conventional Cancer Medicine

We now look at how immunotherapy has been used in conventional cancer medicine. From this discussion, we obtain ideas on how natural compounds might be used to produce some of the same effects on the immune system, and we also see how the use of natural compounds differs from that of most conventional immunotherapy agents. The primary distinction between conventional immunotherapy agents and natural immunostimulant compounds is that the former tend to be cells or cytokines activated or...

Mutations During Carcinogenesis And Progression

Mutations play a critical role in both carcinogenesis and cancer progression, since mutations are the force that initiates a cancer cell, as well as the driving force for their survival and adaptation once formed. Two of the most important consequences of mutations are overexpression of certain genes called oncogenes (onco cancer), which facilitate carcinogenesis and cancer progression, and underexpression of other genes called tumor suppressor genes, which inhibit carcinogenesis and cancer...

Proliferation And Apoptosis In Normal Cells Versus Cancer Cells

All cells in the body at every moment are subject to the dynamic balance that exists between pro-life and pro-death signals. Two very basic pro-life signals are do not die and do proliferate their counterpart pro-death signals are do die and do not proliferate. All of these signals exist more or less simultaneously, and their relative strengths decide a cell's fate. Of these signals, do die and do not proliferate seem to be the defaults. That is, if cells are not told to live, they will undergo...

How Natural Compounds And Chemotherapy Drugs Inhibit Proliferation

Let us now pull together what has been presented about how natural compounds inhibit cancer cell proliferation and compare how natural compounds work to the way current chemotherapy drugs work, thus clarifying what natural compounds have to offer. As we will see, the cancer inhibitory effects of most natural compounds discussed are not due to direct DNA damage, whereas direct DNA damage is an important mechanism for many of the chemotherapy drugs used today. This distinction is important, in...

Estimated Therapeutic and Loael Doses of Melatonin

Melatonin is characterized in this book as an immune stimulant (see Table 1.2), but in addition to immune effects it may also have direct cytotoxic effects against TABLE 22.11 ESTIMATED THERAPEUTIC AND LOAEL DOSES FOR MELATONIN* Required dose as scaled from animal antitumor studies Doses used in human anticancer studies Required cytotoxic dose as determined from pharmacokinetic calculations Target dose based on human studies and pharmacokinetic calculations Minimum required antitumor dose...

Growth Factors

Figure 4.1 illustrates key features of the plasma membrane, including receptor proteins for growth factors. As shown, receptor proteins span the width of the plasma membrane and are therefore able to transfer the signal from growth factors outside the cell to structures within the cell. Once inside the cell, the signal generated at the receptor is transferred to the cell's nucleus by kinase enzymes and other proteins. In many cases, the receptor itself is composed partly of a kinase enzyme....

Glycosidases Proteases And Cancer

As discussed previously, the strength and structure of the ECM is provided by collagen fibers linked together by GAG chains. To break free of the ECM, cancer cells (or cancer-stimulated immune cells) produce enzymes that degrade these ECM components. These enzymes include glycosidases, which break apart GAG chains, and proteases, which break apart protein structures. Many different types of proteases and glycosidases may be involved in cancer invasion, but only two primary ones are discussed...

Estimated Therapeutic and Loael Doses of Curcumin

The estimated required dose of curcumin scaled from animal antitumor studies is different than the estimated dose as calculated from pharmacokinetic and in-vitro data, thus the target human dose is still uncertain and can be estimated only within a large range. The required dose as scaled from animal antitumor experiments is 360 milligrams to 3.2 grams per day similar doses were effective in animal anti-inflammatory experiments. The anticancer dose based on pharmacokinetic calculations is...

Natural Compounds That Suppress The Immune System

Many natural compounds I discuss have the potential to inhibit aspects of the immune system. Although none of these is generally considered a primary immunosup-pressive agent, each can produce immunosuppression as a secondary effect, at least under some circumstances. Natural compounds can induce immunosuppression in many ways, such as by reducing signal transduction (immune cells need signal transduction to function), reducing NF-xB activity, histamine release, vascular permeability, and...

Practical Considerations On Effective Concentrations And Scaling Of Doses

We now turn to two practical considerations identifying effective concentrations and scaling doses from animal studies. Both are mentioned here to give some context for understanding the concentrations and doses reported later in Parts I and II. Concentrations in this book are most commonly reported in micromolar ((M) units, the number of micromoles per liter of solution.a The text may indicate, for example, that a compound inhibits the proliferation of cancer cells at 30 (M. Commonly, this...

Evidence for Synergism Against Cancer Cells

Research already provides evidence that synergistic interactions can occur within combinations of direct-acting natural compounds. Such interactions have been clearly documented by in-vitro studies. In addition, a small number of animal studies have also reported synergistic effects. For example, in three studies in mice, combinations of ATRA and 1,25-D3 synergistically inhibited proliferation of transplanted human breast cancer cells or inhibited angiogenesis induced by cancer cells.3, 4 5...

Macrophages as Inducers and Inhibitors of Angiogenesis

Although it is a common belief that immune activity will inhibit cancer, this simplistic view does not accurately describe what occurs in the body, at least not for macrophages. Macrophages, the predominant immune cell at tumor sites, can both induce and inhibit angio-genesis and tumor progression, depending on the circumstances. That macrophages play a dual role in tumor angiogenesis is not surprising they also do so in wound angiogenesis. Macrophages are the predominant immune cell at wound...

Eicosanoids Prostanoids and Leukotrienes

Eicosanoids were introduced in Chapter 7. There we focused on how prostanoids and leukotrienes are produced from fatty acids, namely via the cyclooxygenase and lipoxygenase pathways, respectively. We also looked at how different fatty acids in the membrane produce different series of prostanoids and leukotrienes, then noted that eicosanoids derived from omega-6 fatty acids facilitate cancer progression and eicosanoids from omega-3 fatty acids inhibit it. We focus here on the role eicosanoids...

Estimated Therapeutic and Loael Doses of Propolis

The estimated required dose of propolis scaled from animal antitumor studies is not in close agreement with that calculated from pharmacokinetic and in-vitro data. This discrepancy suggests an uncertain target human dose that can be estimated only within a large range. The required dose scaled from an animal antitumor ex periment is about 1.3 grams daily, similar to the 0.96 to 11 grams scaled from animal anti-inflammatory experiments. The dose based on pharmacokinetic calculations is much...

Glutathione as a Prooxidant

Disassembling the glutathione molecule at the plasma membrane (before it can enter the cell as individual amino acids) is accomplished by the enzyme GGT (gamma-glutamyl transpeptidase). Ironically, in the process of splitting glutathione, GGT produces a significant amount of hydrogen peroxide. Since cancer cells are generally under oxidative stress and therefore need additional glutathione, many cell lines overexpress GGT. When adequate extracellular glutathione is present, enough hydrogen...

Collagenases and Their Inhibitors

Collagenases are a family of enzymes that digest collagen, the fibrous protein found in connective tissue. Collagen is derived from the Greek words kolla (glue), and gennan (to produce), reflecting its role in gluing cells together. Collagen accounts for approximately 30 percent of the body's total protein store. Each type of collagenase degrades a specific type of collagen. For example, the basement membrane around capillaries contains type IV collagen, and therefore type IV collagenase is a...

Stomach Cancer

In one study, 158 patients with late-stage, postoperative stomach cancer received both chemotherapy and Formula 2. Some patients took the formula for more than four years. The observed 5-year survival rate was 30 percent, with seven patients living longer than 11 years. The 10-year survival rate was 12 percent. Im-munological studies of the survivors revealed an enhancement of both innate and adaptive immunity, including an increase in NK cell function.75,76 The formula contains primarily...

Using Combinations Of Polysaccharides

The dose required for a variety of polysaccharides may range from 2 to 9 grams per day. To achieve this without using excessive amounts of any single herb, combinations of herbs can be used. For example, a decoction comprised of 30 grams of Astragalus and 15 grams of Eleutherococcus contains a polysaccharide dose of roughly 3 grams, assuming that each herb contains about 7 percent polysaccharides. Herbs can also be combined with semi-purified polysaccharides like PSK to achieve the desired...

Adhesion Proteins And Cancer Cell Migration

From the above, it should be clear that production of hyaluronidase or collagenase by tumor cells or other adjacent cells can lead to matrix digestion, which subsequently allows tumor cell invasion. One more aspect of this process is the mechanism by which tumor cells walk during invasion. It is useful to consider the close analogy between the migration of immune cells toward an infection site and the movement of cancer cells away from the central tumor. In both cases, the cells rely on the...

Horse Chestnut

Although horse chestnut has not generally been considered an anticancer agent, one in-vitro study found that horse chestnut saponins are cytotoxic to cancer cells.78 In this book, we include horse chestnut not as a cyto-toxic compound but as one that can protect the vascula-ture and reduce edema. Through these actions, it should be able to inhibit angiogenesis, metastasis, and invasion. Even though anticancer studies on animals and humans have not yet been done, it seems likely that horse...

Ginseng

Some 33 in-vitro studies have been conducted on the effects of ginseng extracts or isolated saponins on cancer cells.89-93 As a whole, these suggest that ginseng or its isolated saponins can inhibit cancer cell proliferation and invasion, usually at 10 to 180 M (for the saponins). Fifteen animal studies have been conducted on the antitumor effects of ginseng extracts or its isolated sapo-nins.94-98 These studies suggest that the extracts and saponins can decrease tumor growth and metastasis and...

Lactic Acid and Insulin

As mentioned, under hypoxic conditions lactic acid may stimulate production of angiogenic factors by macrophages. Unfortunately, few natural compounds have been tested for their effects on lactic acid generation in cancer cells. In one study, apigenin and luteolin inhibited both proliferation and lactic acid release from a human adenocarcinoma cell line in vitro.127 In other studies, the flavonoid quercetin reduced the production of lactic acid in healthy rat cells, probably by blocking the...

P53 Protein as a Transcription Factor

The p53 gene acts as the guardian of DNA, and in the event of DNA damage it performs three crucial functions. First, it halts the cell cycle, for example, by in- a Peptides consist of a few amino acids joined together and proteins consist of manyjoined together. Redox Regulation of Cysteine Disulfide creasing the expression of the p21 gene. Second, it initiates DNA repair. Third, if the DNA cannot be repaired, it initiates apoptosis, for example, by increasing the expression of the Bax gene. To...

Vascular Endothelial Growth Factor

As mentioned in Chapter 7, the rate-limiting step in angiogenesis seems to be increased vascular permeability, and vascular endothelial growth factor (VEGF), one of the most potent inducers of permeability known, plays a key role in angiogenesis. Not surprisingly, some studies have reported that plasma concentrations of VEGF are predictive of recurrence and survival in cancer patients.1 In addition to increased angiogenesis, high concentrations of VEGF have also been associated with increased...

Foreword

As a practicing cancer physician, I find my patients often come to their appointments with a sheaf of papers downloaded from the Internet, seeking guidance. John Boik's previous book, Cancer and Natural Medicine, is dog-eared because it has been a constant source of information in my own practice. I am delighted to add his new book, Natural Compounds in Cancer Therapy, to my shelf it deserves to be included in the personal reference library of every researcher and cancer doctor. But most of...

Seven Strategies For Cancer Inhibition

To be clear, not all cancers develop exactly as in the scenario above. This scenario is common, however, and within it lies the foundation for all our discussions on cancer inhibition. From it, we can identify seven clusters of procancer events 1. Induction of genetic instability. Each cancer cell carries within itself genetic instability, and this instability increases the chances the cell will be able to mutate as needed to adapt to its environment. 2. Abnormal expression of genes. In...