Page 356 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

334 PART III Therapeutic Modalities for the Cancer Patient

the bestseller Spontaneous Healing and director of the Program in When resistance develops to apoptosis-inducing factors, curcumin
Integrative Medicine (PIM) at the University of Arizona in Tuc- can overcome this impediment through alternative cell-signaling
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pathways, such as mitotic catastrophe. Curcumin may also
son, reportedly claimed that black salve cured a tumor on his dog,
VetBooks.ir though his own post is no longer available on this topic. Instead, counteract the induction of prosurvival factors in cells generated
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by RT and chemotherapy.
he now cautions on www.DrWeil.com that the use of blood-
root can cause excruciating pain and tissue degradation. It may Human clinical trials demonstrate no dose-limiting toxicity for
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also leave residual tumor. Over time, the toxicity of bloodroot pure curcumin when given at up to 10 g daily, whether orally
in dogs with cancer has come into focus and their use in cancer (in human studies) or by means of intraperitoneal or intravenous
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patients is now discouraged. administration in rodent-based experimental animal research.
The amount of curcumin contained in turmeric averages only
Boswellia about 3% by weight; concentrated curcumin supplements there-
Boswellic acids exhibit potent antiinflammatory properties in vitro fore supposedly provide higher levels of the active constituent,
and in vivo. Triterpenes in boswellic acid reduce the synthesis provided that the label and actual contents agree. The hurdles of
of leukotrienes in intact neutrophils by inhibiting 5-lipoxygen- maintaining adequate blood levels of curcumin pertain to its low
ase, the key enzyme involved in the biosynthesis of leukotrienes, bioavailability, although absorption varies between species. One
which mediate inflammation. 72,73 Boswellia extracts exert immu- way to overcome delivery challenges could include coupling it
nomodulatory effects by simultaneously inhibiting T-helper 1 with compounds that focus curcumin’s activity toward specific
(Th1) and promoting Th2 cytokine production. They regulate target cells.
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vascular responses to inflammation and stabilize mast cells. In Curcumin could hypothetically negate some of the effects of
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cases of intestinal inflammation, boswellic acids may modulate the chemotherapy because it affects so many pathways. Research sug-
adhesive interactions between leukocytes and endothelial cells by gests that curcumin can inhibit chemotherapy-induced apoptosis in
countering the activation of leukocytes and/or downregulating the breast cancer cells, specifically in combination with camptothecin,
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expression of endothelial cell-adhesion molecules. 76,77 mechlorethamine, or doxorubicin. The potential benefits of cer-
Side effects of boswellic acids may include abdominal discom- tain herbs should be considered and compared against the risks. For
fort, nausea, epigastric pain, and diarrhea. 78 example, a synthetic analog of curcumin helped reduce doxorubicin-
The presence of food in the stomach, and the type of food induced cardiotoxicity through an anticancer–antioxidant dual func-
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eaten, dramatically alters the bioavailability of boswellic acids, and tion in vitro. In addition, curcumin and catechin (from green tea)
bile acids significantly affect their absorption. When human sub- may work synergistically against cancer through cytotoxicity, nuclear
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jects ingest boswellic acids along with a high-fat meal, the area fragmentation, and antiproliferative and proapoptotic effects.
under the plasma concentration—time curves and peak concen-
trations were several times greater than when the herbal prepara- Yunnan Baiyao
tions are taken in the fasting condition. A human study showed Yunnan Baiyao (also known as Yunnan Paiyao) is a Chinese herbal
that the elimination half-life for boswellic acid was approximately mixture consisting primarily of notoginseng that has become a
6 hours, suggesting that oral administration would require dosing popular product among veterinary clients, particularly those car-
every 6 to 8 hours. 79 ing for animals with hemangiosarcoma. This popularity is the
Frankincense extracts, and boswellic acids themselves, dis- result of claims that Yunnan Baiyao regulates bleeding. Therefore
play moderate-to-potent inhibition of human drug-metabolizing patients with a high risk of hemorrhage might be less likely to
CYP450 enzymes, but the potential to cause clinically relevant bleed if Yunnan Baiyao was indeed effective.
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drug—herb interactions is unclear. Westerners first learned of the Chinese herbal mixture “Yun-
nan Baiyao,” meaning “the white medicine of Yunnan,” during the
Curcumin Vietnam War. Members of the US military discovered that prison-
Cancer cells have various methods to evade host defenses. Intui- ers from North Vietnam often carried with them a tiny bottle of
tively, this implies that a drug or herb would work best against this product to take in the event that they were injured and bleed-
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cancer when it has more than one mechanism of action against ing, either internally or externally. Over the ensuing decades,
the disease. Curcumin, a bioactive component of the spice tur- Yunnan Baiyao has grown in popularity among complementary
meric, has been shown to have several mechanisms of action. 81,82 medical practitioners and even in some conventional medicine
It induces phase II detoxification enzymes, suppresses tumor cell practices for its hemostatic and thrombolytic properties. 94
proliferation in several cancer cell lines, and downregulates tran- The Chinese doctor Qu Huangzhang developed Yunnan Baiyao
scription factors (nuclear factor κB [NFκB], activator protein 1 in the Yunnan province of China in the early 1900s. The Yunnan
[AP-1], and early growth response 1 [EGR-1]). 83,84 Curcumin province is known as “the Kingdom of Fauna and Flora” for its vast
also downregulates enzymes such as cyclooxygenase-2 (COX-2), supply of plants and animals used in Chinese medicinals. Although
lipoxygenase (LOX), nitric oxide synthase (NOS), matrix metal- the capsule’s contents were kept secret until relatively recently, sus-
loproteinase 9 (MMP9), and urokinase-type plasminogen activa- picion grew that its main active ingredient consisted of pseudo-
tor; it also limits production of tumor necrosis factor, chemokines, ginseng root, now called Panax notoginseng, notoginseng, “tien chi,”
cell surface adhesion molecules, and growth factor receptors (e.g., or “san qi.” Notoginseng is a type of ginseng that offers the highest
epidermal growth factor receptor [EGFR], human EGFR 2 concentration of hemostatic constituents among all seven major
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[HER2]). Curcumin may have antiangiogenic effects and may ginseng types. Notoginseng from the Yunnan outperforms that
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alter the cytotoxicity of certain chemotherapy drugs. 87,88 grown elsewhere in terms of crop yield and quality. Other sub-
Curcumin causes cell death in several human cancer cell stances in Yunnan Baiyao formulations vary between manufactur-
lines, including breast, lung, prostate, colon, melanoma, kidney, ers and may include myrrh, ox bile, Chinese yam, sweet geranium,
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hepatocellular, ovarian, and leukemia. Curcumin produces cell lesser galangal root, and possibly other antiseptics or astringent
death through both apoptotic mechanisms and alternative means. substances in a starch base. Some preparations of Yunnan Baiyao