A large number of natural compounds can stimulate or support the immune system or do both. A selected list of some of the major compounds is provided in Table 12.1. Note that many other natural compounds discussed in this book (and many not included) could act as immunostimulants or supportive agents. For example, CAPE has been reported to increase the susceptibility of tumor cells to NK cell attack and induce expression of tumor-associated antigens on human melanoma and brain cancer cells lines in vitro.1,2 As another example, oral administration of proanthocyanidins to mice has increased NK cell cytotoxicity and enhanced ex-vivo IL-2 production by immune cells.3 Even though not comprehensive, Table 12.1 does include many of the well-known natural immunostimulants and supportive compounds. Reference books that discuss additional natural compounds with these effects are cited in Chapter 16.
In addition to stimulating the immune system, we must also inhibit immune evasion. One primary way cancer cells evade immune attack is by producing excessive amounts of immunosuppressive substances like PGE2 and immunosuppressive cytokines, such as transforming growth factor-beta and IL-10. Natural compounds that reduce production of TGF-beta and/or IL-10 include PSK and other polysaccharides, proanthocyanidins, omega-3 fatty acids, monoterpenes, and vitamin E 3-11 In addition, protein kinase inhibitors like genistein can reduce the signaling effects of IL-10.12 Natural compounds that inhibit PGE2 production include omega-3 fatty acids and other compounds discussed in Chapter 8 (see Table 8.2). Lastly, compounds that reduce vascular endothelial growth factor production (see Chapter 8)
TABLE 12.1 NATURAL COMPOUNDS THAT ASSIST THE IMMUNE SYSTEM
HERBAL IMMUNOSTIMULANT COMPOUNDS
Astragalus membranaceus Eleutherococcus senticosus Ganoderma lucidum Panax ginseng
Shiitake (Lentinus edodes), PSK, and other mushroom polysaccharides
ANTIOXIDANTS AND NUTRITIONAL COMPOUNDS
Glutathione-enhancing compounds (i.e., most antioxidants)
Bromelain and other enzymes Melatonin
Note: See Table H. 1 in Appendix H for details and references.
may limit immune evasion by cancer cells. In addition to its role in increasing vascular permeability, VEGF may also impede maturation of dendritic cells and thereby reduce the presentation of tumor antigens to lymphocytes.13 Thus, between compounds that stimulate and/or support the immune system and those that limit immune evasion, we see that a large number, if not the majority of compounds discussed in this book, could affect tumor progression via immune-mediated mechanisms.
The compounds listed in Table 12.1 are divided into three categories: herbal immunostimulant compounds, antioxidants and nutritional compounds, and others. After discussing them, we look at some Chinese studies that have used herbal immunostimulants in cancer treatment.
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