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Cancer Adjuvant Therapy
Curcumin
Worldwide clinical trials have chiseled out a definite place for curcumin
in oncology. Among them are New York Presbyterian Hospital and the Weill
Medical College, which reported that curcumin, a curcuminoid found in
turmeric, directly inhibited the COX-2 enzyme (Zhang et al. 1999). So
excited are various oncologists regarding curcumin that the potent anti-inflammatory
has been classed as a potential third generation cancer chemopreventive
agent.
Curcumin inhibited thromboxane A2 (TxA2), a highly unstable, biologically
active compound created by COX from AA (Shah et al. 1999; Newmark et al.
2000). Unless controlled, TxA2 promotes tumor endothelial cell migration
(metastasis) and angiogenesis. By inhibiting TxA2, curcumin reduces the
tumor's blood supply and lessens the threat of metastasis (Arbiser et
al. 1998; Nie et al. 2000). Curcumin is effective at inhibiting 5-lipoxygenase
and subsequently HETE, a survival factor for prostate, breast, and pancreatic
cancers (Ghosh et al. 1998; Ding et al. 1999; Newmark et al. 2000; Li
et al. 2001).
The following list illustrates the depth of curcumin's defenses against
cancer:
- Colon: Curcumin inhibited chemically induced carcinogenesis in the
colon when administered at different stages of the cancer process. Laboratory
rats, administered curcumin during either initiation or late in the
premalignant phase, had a lesser incidence and fewer numbers of invasive
malignant colon tumors (Kawamori et al. 1999). Also, by inhibiting COX-2-arachidonic
acid interactions, curcumin suppresses prostaglandins responsible for
inflammatory processes (Plummer et al. 1999). Chronic inflammation has
for decades been regarded as a cause of colon cancer (Konig et al. 1976).
- Antioxidant activity: Curcumin inhibits or possibly even reverses
oxidative damage by scavenging and neutralizing free radicals. By defusing
the hydroxyl and superoxide radicals and breaking oxidative chain reactions,
curcumin protects DNA with greater efficiency than lipoic acid, vitamin
E, or beta-carotene (Ruby et al. 1995; Ahsan et al. 1999; Li et al.
2001).
- Breast cancer: Curcumin inhibits the growth of multiple breast cancer
cell lines (Inano et al. 1999), particularly those that result from
exposure to environmental estrogens such as chemicals and pesticides
(Verma et al. 1998). Also, curcumin, estrogen, and estrogen mimickers
gain entry into the cell through the aryl hydrocarbon receptor. Because
curcumin competes for entry, it can crowd out damaging materials (Ciolino
et al. 1998). According to researchers, curcumin blends well with other
cancer inhibitors. For example, a curcumin-isoflavonoid combination
suppressed the growth of estrogen receptor-positive cancer cells up
to 95% (Verma et al. 1998).
- Oral tumors: Curcumin inhibits oral squamous cell carcinoma more
effectively than either genistein or quercetin (Ellatar et al. 2000).
Only cisplatin, a platinum-based chemotherapy drug, was more effective.
- Skin tumors: Curcumin inhibits skin tumors. When applied topically,
curcumin reduces skin inflammation and inhibits local swelling (Huang
et al. 1997).
- Prostate cancer: Curcumin was able to decrease the proliferative
potential of androgen-independent prostate cancer cells--and cells of
other androgen-dependent cancers--largely by encouraging apoptosis.
Moreover, a significant decrease in microvessel density, the sustaining
blood supply of a tumor, was also observed (Dorai et al. 2001).
- Leukemia: Curcumin-induced apoptotic cell death in promyelocytic
leukemia HL-60 cells at concentrations as low as 3.5 mcg/mL (Kuo et
al. 1996).
- Protein kinase C (PKC) and epidermal growth factors (EGF): Curcumin
was proclaimed "potentially useful" in developing anti-proliferative
strategies to control tumor growth by suppressing the activity of protein
kinase C (PKC) (Korutla et al. 1995). As the activity of PKC is slowed
down, tumor proliferation is halted (Lin et al. 1997). PKC transmits
signals from the epidermal growth factor receptor (EGF-R), a cycle that
ultimately encourages the growth of tumors. Conversely, cancers awaiting
EGF stimulation are dealt a severe blow if this pathway is severed.
Curcumin blocked the activation of EGF by 90%.
- p53 potentiator: Curcumin increases expression of healthy nuclear
p53 protein in human basal cell carcinomas, hepatomas, and leukemia
cell lines (Jee et al. 1998). Turn to the protocol Cancer: Gene Therapies,
Stem Cells, Telomeres, and Cytokines to read more about tumor suppressor
genes.
- Tumor necrosis factor-alpha (TNF-alpha): Researchers at the University
of Kentucky showed that TNF-alpha acts as a catalyst in cytokine production,
stimulating interleukin-6 (IL-6) and -8 (IL-8) and activating NF-kB
(Blanchard et al. 2001). Curcumin inhibits TNF-alpha, thus blocking
TNF-alpha, NF-kB pathways, and the emergence of pro-inflammatory cytokines
(Xu et al. 1997-1998; Li et al. 2001; Literat et al. 2001). To read
more about proinflammatory cytokines, turn to the protocol Cancer: Gene
Therapies, Stem Cells, Telomeres and Cytokines.
- Helicobactor pylori: Exposure of gastric epithelial cells to the ulcer-causing
bacterium H. pylori (considered a potential gastric and pancreatic carcinogen)
induces secretion of IL-8. IL-8 plays a pivotal role in the development
of cancer. The more virulent H. pylori, the greater the production of
IL-8. H. pylori strains that fail to induce IL-8 secretion do not activate
NF-kB, while all IL-8 inducing strains activate the transcription factor.
Curcumin is capable of inhibiting NF-kB and completely suppressing IL-8.
By restraining essential players in the development of H. pylori, curcumin
diminishes the risks of both gastric and pancreatic cancer (Munzenmaier
et al. 1997; Stolzenberg-Solomon et al. 2001).
Although the benefits of curcumin are impressive, curcumin is poorly
assimilated. This means that while the digestive tract and liver profit,
the remainder of the body may be denied benefit. Administering 2000 mg
of curcumin showed that very little reached the bloodstream. This dilemma
is amendable by adding a small amount of piperine (a component of black
pepper) to curcumin, increasing bioavailability by 2000% (Shoba et al.
1998). However, it is possible that piperine in combination with prescription
drugs could increase the bioavailability of the drug. Therefore, it is
recommended that curcumin (containing piperine) be taken 2 hours apart
from prescription medications.
Super Curcumin dosage: Healthy people typically take 900 mg of curcumin
each day. Cancer patients often take as much as four 900-mg capsules 3
times a day for a 6- to 12-month period, reducing the dosage thereafter.
Individuals with biliary tract obstruction should avoid curcumin because
it enhances biliary flow from the liver. High doses of curcumin should
not be taken on an empty stomach to protect against gastric irritation.
Note: The
question ultimately arises as to whether curcumin is appropriate during
chemotherapy. A recent study from the University of North Carolina (Chapel
Hill) showed that curcumin reduced the effectiveness of chemotherapy in
breast cancer patients by inhibiting reactive oxygen species (Somasundaram
et al. 2002). Please refer to the protocols Cancer:
Should Patients Take Dietary Supplements? and Cancer
Chemotherapy to read more about this study and the advisability of
taking curcumin during conventional treatment.
Dimethyl Sulfoxide (DMSO)
In August 1995, Dr. Julian Whitaker, M.D., relayed his own experience
with DMSO, when a basal cell carcinoma (about the size of a dime) appeared
on his ear. A dermatologist recommended surgical removal of the cancerous
portion and a skin graft replacement. Instead, Dr. Whitaker made a paste
from shark cartilage, vitamin C, and DMSO and applied the mixture to the
lesion daily. Within 3.5 weeks, the basal cell had completely disappeared.
Stanley Jacob, M.D., professor at the Oregon Health Sciences University
(Portland) suspected DMSO was the hero, although Dr. Whitaker has confidence
in the full formula (Whitaker 1995).
The Sealy Center for Molecular Sciences reported that DMSO, administered
either before or 15 minutes after TNF-alpha, blocked 80% of NF-kB. By
suppressing TNF-alpha and NF-kB, DMSO broke an inflammatory cascade that
otherwise terminates in an onslaught of potentially damaging cytokines
(Vlahopoulos et al. 1999).
DMSO is an excellent transporter of other therapies into cancerous cells.
In fact, many offshore cancer clinics consider it the standard for all
patients who are undergoing various therapies.
Essential Fatty Acids (EFAs)--
block arachidonic acid, inhibit COX-2 enzyme, regulate cell division and
inhibit adhesion, prevent cachexia, potentiate traditional cancer therapies,
and suppress the activity of pro-inflammatory cytokines
As a result of the current fat phobia, over 80% of Americans consume inadequate
amounts of essential fatty acids (especially omega-3 fatty acids). Physicians
report that this scarcity is contributing to epidemic proportions of degenerative
diseases, including cancer (Murray et al. 1996). The omega-6 to omega-3
fatty acid ratio typically seen may be as high as 20:1, whereas the optimal
ratio may be nearer 1:1 (Mercola 2002a). EFAs, although not manufactured
by the body, perform vital functions that prevent and control cancer.
- As enzymes metabolize AA, the byproducts of the metabolism fuel the
cancer process (Comprehensive Cancer Care 2001). Oxidized AA is, in
fact, considered a primary initiator of cancer (Newmark et al. 2000).
One gram of omega-3 fatty acids blocks 10 grams of AA (Pizzorno 2001).
- The COX-2 enzyme (interacting with AA) can cause excess production
of PGE2, promoting cancer cell growth. Eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA) (derived from alpha-linolenic acid or fish
oil) are effective COX-2 inhibitors (Ringbom et al. 2001).
- Fish oil is the most documented supplement to suppress (up to 90%)
a cascade of damaging cytokines, including TNF-alpha and IL-1 (James
et al. 2000). It should be noted that psychological stress induces the
production of pro-inflammatory cytokines, such as TNF-alpha, IL-6, and
IL-10. Increasing omega-3 fatty acids lessened the pro-inflammatory
response to psychological stress (Maes et al. 2000). For information
regarding a blood test to obtain a cytokine profile, call (800) 208-3444.
- Women with high levels of alpha-linolenic acid in breast tissue have
a 60% lower risk of breast cancer compared to women with low levels
(Klein et al. 2000; Maillard et al. 2002). Jeffrey Bland, esteemed scientist
and teacher, reported a supportive study involving 500 (C3H) mice prone
to breast cancer. The mice were divided into 10 groups of 50 animals
and evaluated regarding the impact of various dietary oils on the occurrence
of cancer. One-tenth of the animals received standard chow and served
as a control group; another group received standard chow plus benzanthracene,
a carcinogen. The other eight groups received isocaloric diets along
with the cancer inducer; the variable was the type of fat (not the amount)
fed in conjunction with the chow. Eight oils were evaluated: tallow,
fish, corn, primrose, safflower, linseed oils, and two others. At the
conclusion of the study, eight of the 10 groups (400 animals) were dead
with mammary cancer. The 100 survivors were animals fed omega-3 rich
oils. The study was repeated using different types of oils and varying
amounts of the cancer inducer. The end results werethe same. Researchers
postulated that the advantage of omega-3 fatty acid was the oil's ability
to reduce inflammatory mediators, those signaling tumor progression
and metastasis (Cameron et al. 1989).
- Epidemiologic and experimental studies suggest that oils rich in
omega-3 fatty acids lessen the risk of colon cancer. A relatively small
fraction of alpha-linolenic-rich perilla oil (25% of total dietary fat)
provided an appreciable beneficial effect in reducing cancer risk (Narisawa
et al. 1994).
- Low EFA status results in a lack of oncogene control with a shift
toward cell proliferation (Pizzorno 2001). EFAs also regulate the adhesiveness
of cancer cells, including cell-cell and cell-matrix adhesions (Jiang
1998).
- Fatty acids, particularly EPA, inhibited the growth of three human
pancreatic cancer cell lines (MIA PaCA-2, PANC-1, and CFPAC), suggesting
therapeutic benefit to pancreatic cancer patients (Falconer et al. 1994).
- Omega-3 fatty acids prevent cachexia (the muscle wasting and weight
loss that occurs in some cancer patients irrespective of proper nutritional
intake). Controlling the symptoms common to cachexia (anorexia, abnormal
macronutrient metabolism, and fatigue) improves quality of life and
extends periods of remission (Bruera 2003).
- Researchers found DHA and EPA cytotoxic to myeloma cells in vitro
(Sravan et al. 1997). Individuals who regularly consume fish and cruciferous
vegetables appear to lessen their risk of developing multiple myeloma
(Brown et al. 2001).
Thirty-two dogs with Stage III lymphoma and their response to a dietary
and chemotherapeutic regime were evaluated. All of the animals were fed
identical diets, but they received varying types of oils. For example,
one group received menhaden fish oil (rich in omega-3 fatty acid) and
arginine, while the control group received soybean oil (Ogilvie et al.
2000). The animals also received doxorubicin every 3 weeks.
As DHA and EPA levels increased in the test group, the animals experienced
longer disease-free intervals and subsequently increased survival time.
Dogs receiving the supplemented diet lived about 700 days; animals receiving
the soybean oil lived only about 400 days. The time until relapse was
also significant: 425 days in the treatment group versus 275 days in the
control group. Note: Since fish oil increases the effectiveness of chemotherapeutic
agents, the animals receiving the menhaden oil realized an additional
advantage over the soybean-treated animals (Hardman et al. 2001).
Suggested dosages for various EFAs: Take six 1000-mg capsules a day of
perilla oil, which provide 550-620 mg of alpha-linolenic. Flaxseed oil,
1000-mg softgels, is a rich source of omega-3 fatty acids. Take 7 softgels
a day. A preventive dose of a fish oil concentrate called Mega EPA is
4 capsules a day (2800 mg of EPA/DHA). Cancer patients often use 8-12
Mega EPA softgels daily along with 4 Mega GLA softgels to balance the
high amount of omega-3 being consumed in the fish oil. Another option
for cancer patients is 8 capsules a day of Super GLA/DHA, providing a
highly concentrated amount of DHA, GLA, and a moderate amount of EPA.
Higher dosages should be physician supervised.
Garlic (Allium sativum)--is inhibitory to a number of malignancies, minimizes
damage imposed by known carcinogens, and boosts the immune system
No plant has the medicinal history, spanning as many cultures, of garlic.
Garlic, in fact, appears to be the quintessential medicine/food, having
influence on simplistic diseases from common colds to degenerative diseases.
For centuries the Chinese have used garlic-containing herbal formulas
to treat tumors, but scientists were challenged to find the mechanism
that rendered it efficacious.
Among those dedicated to validating garlic is Dr. Benjamin Lau, M.D.,
Ph.D. Dr. Lau, focusing upon cancer biology and immunology, was motivated
by an epidemiological study reported by the People's Republic of China.
The study compared two large populations in the Shandong Province: Cangshan
Country and Qixia Country (Mei et al. 1982). Residents of Cangshan County
experienced the lowest death rate due to stomach cancer (three per 100,000),
regularly consuming about 20 grams of garlic a day; the people of Qixia
had a 13-fold higher stomach cancer death rate, eating garlic only rarely.
It appears that lowering nitrite concentrations may be the protective
mechanism resulting in fewer numbers of gastric cancers. Jhinzou Liu,
Ph.D., a Chinese biochemist, found garlic "much more effective than
vitamin C" in keeping nitrosamines, potentially carcinogenic compounds,
from forming.
Garlic's anticarcinogenic effects are not restricted to gastric malignances.
- Garlic (administered intralesionally to mice) was significantly more
effective than BCG (bacillus Calmette-Guerin), a weakened form of the
tuberculosis bacilli, in treating bladder cancer (Lau et al. 1986).
- Garlic extract reduced the incidence of breast cancer (in mice) by
70-90% (Langer 1991).
- Diallyl disulfide, a sulfur compound, induced cell death (apoptosis)
in non small cell lung cancer cells (Hong et al. 2000); Diallyl sulfide,
a component of garlic oil, inhibited liver carcinogenicity following
carcinogenic exposure (Hayes et al. 1987); S-allyl cysteine, (a derivative
of aged garlic extract), inhibited human neuroblastoma cell growth in
vitro (Welch et al. 1992); allixin, one of the compounds of aged garlic
extract, inhibited the development of skin cancer (Nishino et al. 1990).
Diallyl sulfide was highly inhibitory during the initiation phase of
esophageal cancer (Wargovich et al. 1992).
- S-allyl cysteine (SAC) inhibited proliferation and cell growth of
nine human and murine melanoma cell lines, producing positive results
without side effects (Takeyama et al. 1993). Of equal importance, garlic
modulated major cell differentiation markers of melanoma. As the cell
shows distinguishable characteristics (differentiation), it eventually
loses its uncontrollable propensity to divide.
- S-allyl cysteine and diallyl sulfide reduced colonic damage and the
incidence and frequency of colon tumors if administered 3 hours prior
to each carcinogenic injection. Colonic damage was inhibited by 36%
and 47% respectively (Sumiyoshi et al. 1990). Michael Wargovish, M.D.
(Houston), claims that diallyl sulfide is one of the most active chemopreventive
agents known.
S-allyl cysteine (SAC) appears to be able to overcome the adverse side
effects (heart and liver damage) associated with the chemotherapeutic
agent doxorubicin. Doxorubicin resulted in a 58% mortality rate among
laboratory mice; SAC reduced doxorubicin-induced mortality to 30% (Mostafa
et al. 2000). Weight loss, typical with doxorubicin, was reduced from
13% to 9% with SAC.
Certain garlic constituents possess antioxidant properties, while other
constituents act as oxidants. The latter case is strikingly demonstrated
when human hemoglobin is mixed with extracts from fresh garlic and from
dried raw garlic powder products. The hemoglobin-garlic extract mixtures
turn dark, and their spectra reveal the oxidation of hemoglobin to methemoglobin.
Contrarily, extracts from aged garlic do not cause oxidative changes.
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