Histamine is generated by mast cells in response to tissue injury and other factors.a Mast cells migrate toward tumors in response to growth factor production, and once at the site, the histamine they release increases
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vascular permeability and stimulates angiogenesis. ,
Numerous natural compounds inhibit the release of histamine from mast cells. This release is referred to as mast cell "granulation," since histamine is stored in in-tracellular pouches called granules. Natural compounds that inhibit mast cell granulation are listed in Table 8.3. Note that many of these compounds occur in traditional herbal formulas used to treat asthma and allergies, which are diseases mediated by histamine release. Some compounds listed in the table are PTK inhibitors, which have been reported to inhibit histamine release from mast cells in some circumstances.124,125 PKC inhibitors may also inhibit histamine release.126 Apigenin, luteolin, and EGCG are PTK and PKC inhibitors, and genistein inhibits PTK.
A second method of reducing histamine secretion is to inhibit mast cell migration. This prevents mast cells from reaching an inflamed area and releasing histamine there. Mast cells are attracted to growth factors such as VEGF, PDGF, EGF, and bFGF, so again, inhibitors of these compounds may reduce angiogenesis. Mast cell migration can also be reduced by compounds that inhibit NF-kB activation and PTK activity, both of which inhibit VEGF, PDGF, EGF, and/or bFGF production.
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