Berberine: Berberine is an alkaloid found in various
different medicinal herbs. Probably the most popular herb containing
berberine is Goldenseal (
Hydrastis Canadensis), followed by Oregon grape (
Berberis aquifolium) and Chinese Isatis (
Isatis tinctoria).
A 1990 study tested the tumor-killing effect of berberine compared to the chemotherapy drug BCNU (
carmustine)
in both glioma cell cultures and in rodents implanted with tumors.
Berberine alone produced a 91% kill rate in cell cultures, compared to
43% for BCNU. Combining berberine with BCNU yielded a kill rate of 97%
(Zhang, RX et al 1990).
A 1994 paper described
in vitro experiments using berberine
alone, or in combination with laser treatments, on glioma cells. The
combination was especially effective, suggesting “the possibility of
berberine as a photosensitive agent” (Chen KT et al 1994).
A 2004 paper tells us that berberine increases the benefit of
radiation treatment by making glioblastoma cells more sensitive to
radiation damage, without affecting healthy brain cells (Wallace J et al
2004). A similar effect is seen in lung cancer wherein berberine
sensitizes lung tumor cells to radiation (Peng PL et al 2008, Liu Y et
al 2008).
Berberine slows
the spread of
nasopharyngeal
carcinoma, decreasing motility of the tumor cells (Liu SJ et al 2008).
Berberine inhibits gene expression and enzyme activity necessary for
glioblastoma and astrocytoma growth (Wang DY et al 2002). It also
inhibits an enzyme called arylamine N-acetyltransferase (NAT). NAT may
initiate cancer and has been correlated with the carcinogenic effect of
heterocyclic aromatic amines, the kind of chemicals formed when red meat
is cooked (Hung CF et al 2000).
The scientific understanding of how berberine actually works
continues to advance. A 2007 description suggested that berberine acts
“through several ways, such as regulating apoptotic gene expression,
suppressing the formation of tumor angiogenesis [and] blocking signal
transduction pathway” (Yang J et al 2007). A 2008 study explained that
berberine triggers apoptosis in glioblastoma cells through the
mitochondrial caspases pathway (Eom KS et al 2008). As of 2009, research
reported that berberine kills glioma cells through several mechanisms:
“Cytotoxicity is attributable to apoptosis mainly through induced
G2/M-arrested cells, in an ER-dependent manner, via a
mitochondria-dependent caspase pathway regulated by Bax and Bcl-2” (Chen
TC et al 2009).
In 2010 explanations for action expanded to include the
inhibition of NF-KappaB and the reduction of a series of chemicals that
help cancer cells to survive, including one called survivin (Pazhang Y
et al 2010). Survivin slows down apoptosis, allowing tumor cells to
survive. Healthy cells do not produce survivin but cancer cells
typically do (Pandey MK et al 2008).
Several hundred published papers suggest that berberine is effective
against not only brain tumors but a range of cancers. In the last few
months alone, several interesting papers have been published. Among
their conclusions are: berberine prevents cell growth and induces
apoptosis in breast cancer cells (Kim JB et al 2010; Patil JB et al
2010); berberine is cytotoxic to cervical cancer cells (Lu B et al
2010); berberine inhibits cell growth in pancreatic cancer cells by
inducing DNA damage (Pinto-Garcia L et al 2010); and berberine triggers
cellular suicide in tongue cancer (Ho YT et al 2009).
Boswellia: The resin from
Boswellia serrata also
has an important role in treating brain cancer. Boswellia is commonly
used for treating inflammation because it acts as an NF-KappaB
inhibitor. It is neuroprotective, anti-inflammatory, and reduces anxiety
(Moussaieff A et al 2009).
One important use of boswellia is in the treatment of traumatic brain
injuries. Boswellia decreases the brain swelling from glioblastoma,
allowing a decrease in the use of
prednisone and thus reducing its side effects (Janssen G et al 2000).
Boswellia inhibits hippocampal neurodegeneration and exerts a
beneficial effect on functional outcome after closed head injury, as
evidenced by reduced neurological severity scores and improved cognitive
ability in an object recognition test (Moussaieff A et al 2008).
A 2006 paper reports that
Boswellia serrata was gaining
importance in the treatment of edema surrounding tumors and other
chronic inflammatory diseases. This study suggested that boswellia might
be considered as an alternative to corticosteroids in reducing cerebral
peritumoral edema (Weber CC et al 2006).
Finding ways to reduce or replace steroid use in the treatment of
brain tumors is important, since steroid drugs may protect brain tumor
cells. According to a 2000 article in
Neuroscience,
“glucocorticoids are often used in the treatment of gliomas to relieve
cerebral oedema, the inhibition of apoptosis by these compounds could
potentially interfere with the efficacy of chemotherapeutic drugs.”
(Gorman AM et al 2000)
A 2006 study reported that steroids interfere with glioma cell
apoptosis (NĂ Chonghaile T et al 2006). Steroids block the
cancer-killing action of
camptothecin, a chemotherapy drug used in treating glioma (Qian YH et al 2009).
Boswelliamay be doubly useful for primary brain tumors. Studies
published in 2000 (Winking M et al 2000) and 2002 (Park YS et al 2002)
tell us that in addition to helping reduce cerebral swelling around the
tumor, boswellia also kills glioblastoma cells in a dose-dependent
manner.
Boswellia is also useful for treating secondary brain tumors. In 2007
researchers reported using boswellia to treat a patient with breast
cancer metastasis to the brain. Familiar with the German research on
using boswellia in the treatment of primary brain tumors, the team tried
it with these secondary brain tumors and reported benefit. After ten
weeks of boswellia treatment in combination with radiation treatment,
all signs of brain metastases on the patient’s CT scans had disappeared
(Flavin DF 2007).
Curcumin: Curcumin is extracted from turmeric rhizomes (
Curcuma longa),
a plant that has been eaten for thousands of years. As of this writing,
the National Institute of Health’s website, PubMed, lists 1,335
published papers on curcumin and cancer in the peer-reviewed scientific
literature.
A growing number of these studies focus specifically on using
curcumin in connection with brain cancer. A 2006 paper tells us curcumin
suppresses growth of glioblastoma by triggering the apoptotic pathways
that destroy glioblastoma cells (Karmakar S et al 2006). Curcumin turns
off the signals in the cells that protect glioblastoma cells from
apoptosis, allowing the suicide process to destroy the cancer cells
(Karmakar S et al 2007, Luthra PM et al 2009).
Curcumin has a similar action against other brain tumor types,
including meduloblastoma cells and pituitary cancers (Bangaru ML et al
2010, Elamin MH et al 2010). Curcumin inhibits pituitary cancer from
forming (Schaaf C et al 2010). It also slows growth of pituitary tumors
and inhibits production of excess pituitary hormones by tumors (Schaaf C
et al 2009, Miller M et al 2008).
Curcumin’s mechanisms of action are complex. It acts through multiple
pathways, interfering with cancer growth and stimulating cancer
destruction (Choi BH et al 2008). Curcumin decreases Glial cell
line-derived neurotrophic factor (GDNF), a chemical that promotes tumor
migration and invasion (Lu DY et al 2010, Song H et al 2006). It also
acts as an angiogenesis inhibitor (Perry MC et al 2010).
An article in Brain Research confirms that curcumin crosses the blood
brain barrier; thus reaching the brain and any tumor cells there
(Purkayastha S et al 2009). A study published in the Journal of Neurochemistry reported that
curcumin sensitized glioma cells to several of the chemotherapy drugs
often utilized to treat brain cancers (
cisplatin,
etoposide,
camptothecin, and
doxorubicin)
as well as to radiation. “These findings support a role for curcumin as
an adjunct to traditional chemotherapy and radiation in the treatment
of brain cancer” (Dhandapani KM et al 2007).
Curcumin has long been known for poor bioavilability, requiring high
doses to achieve desired blood levels. A novel curcumin formulation,
BCM-95
®, has been developed. It delivers up to seven times
more bioactive curcumin to the blood than earlier curcumin formulations.
Human evidence for the increased bioavailability of BCM-95
®
was published in a 2008 study in the Indian Journal of Pharmaceutical
Science (Antony B et al 2008). An earlier animal trial was published in
Spice India in 2006 (Merina B et al 2006).
Other Natural Ingredients
Quercetin: Quercetin enhances glioma cell death
(Siegelin MD et al 2009). While killing cancer cells, quercetin protects
healthy brain cells (Braganhol E et al 2006).
An especially interesting study tested a combination of quercetin and the chemotherapy drug
temozolomide
(Temodar®) on astrocytoma tumor cells. Temozolomide is commonly used
for the treatment of glioma in conjunction with radiation therapy. This
drug typically kills brain tumor cells by triggering a process called
autophagy, while quercetin promotes necrosis in a dose dependent manner.
This study reported for the first time that quercetin combined with
temozolomide was much more effective in inducing apoptosis, programmed
cell death, in glioma cells than was either substance alone. To quote
the authors, “Our results indicate that quercetin acts in synergy with
temozolomide and when used in combination rather than in separate
pharmacological application, both drugs are more effective in programmed
cell death induction. Temozolomide administered with quercetin seems to
be a potent and promising combination which might be useful in glioma
therapy” (Jakubowicz-Gil J, et al 2010).
Resveratrol: Resveratrol also strongly inhibits
brain tumor cells (Leone S et al 2008, Shao J et al 2009, Gagliano N et
al 2010). Quercetin and resveratrol, when taken together “presented a
strong synergism in inducing senescence-like growth arrest. These
results suggest that combining these polyphenols can potentiate their
antitumoral activity, thereby reducing the therapeutic concentration
needed for glioma treatment” (Zamin LL et al 2009).
Green Tea and Coffee: People who drink five cups per day of tea or coffee are 40% less likely to get glioma (Holick CN et al 2010). A 2006 study informed us that the EGCG in green tea reduces the
radio-resistance of glioblastoma cells potentially increasing the
benefit of the standard radiation and chemotherapy treatment of this
cancer (Karmakar S et al 2006).
Caffeine, found in significant quantities in coffee and green tea,
inhibits migration of glioblastoma cells and increases survival (Kang SS
et al 2010). It also makes glioma cells more sensitive to ionizing
radiation and chemotherapy (Sinn B et al 2010). Caffeine enhances the
effect of temozolomide in radiation treatments (Chalmers AJ et al 2009).
At least part of the explanation for these benefits is that coffee is
a peroxisome proliferator-activated receptor (PPAR) gamma agonist (Choi
SY et al 2007). PPAR gamma agonists inhibit brain tumor growth and
possibly even brain cancer stem cells (Grommes C et al 2010, Chearwae W
2008).
Sulforaphane: Sulforaphane is one of the active
compounds in cruciferous vegetables, especially broccoli, responsible
for their anti-cancer action. It has been shown to confer
neuroprotection and preserve blood-brain-barrier integrity in animal
models (Dash PK et al 2009).
Sulforaphane activates “multiple molecular mechanisms for apoptosis
in glioblastoma cells following treatment” (Karmakar S et al 2006). Resveratrol and sulforaphane act synergistically against brain tumor
cells. A 2010 article states, “Combination treatment with resveratrol
and sulforaphane inhibits cell proliferation and migration, and reduces
cell viability. Resveratrol and sulforaphane, may be a viable approach
for the treatment of glioma.” (Jiang H et al 2010)
Source:
http://www.lef.org/protocols/cancer/brain-tumor/page-02
