rexresearch
Mebendazole vs Cancer
http://www.viewzone.com/mebendazole.html
Mebendazole -- Inexpansive
Cancer Cure?
by Dan Eden
Good News!
Ordinarily, an article like this might not appeal to someone
with a minimal interest in biology. But this article is about
cancer. That's something that we will all experience, either
personally or with someone close to us.
I'm not going to bore you with statistics or preach about
unhealthy lifestyles or genetics. The fact is that we all get
cancer in our lifetime -- probably many times. Our bodies
usually defend against the cancerous cells and they are
destroyed before they can do any damage. Unfortunately, for some
people, the battle isn't so easy and the outcome unclear.
But wait... there is good news. It's a medicine that seems too
good to be true, yet it is. And get this -- it costs just a
couple of dollars and its in most every local pharmacy. It's
anti-cancer success has been well documented in journals (which
I will show you) -- even with cancers that are unresponsive to
other chemotherapy. While it kills cancer cells it poses no harm
to the normal cells and has little or no side effects. It's
called mebendazole and "Big Pharma" hopes you will never hear
about it.
Mebendazole (MBZ)
If you have ever cared for young children then you are probably
familiar with this medicine under the name of Vermox, Ovex,
Antiox, and Pripsen. It is usually prescribed to treat pinworms,
roundworms, whip worms and hookworms -- organisms that find an
unwelcome home in our intestines. For some time now, scientists
have known how it works, but the method of death meted out to
the targeted parasites was of little interest to them. But that
has since changed.
How it works...
This next part gets a little technical. I'll try to explain
things in a general way. I'm by no means a scientist or
biologists but I'll share with you what I have learned.
One of the misconceptions that people have about a cell is that
it contains a nucleus, a cell wall and everything inside
(cytoplasm) kind of sloshes around in a liquid or gel. In fact,
the inside of a cell contains a kind of scaffold made of
micro-tubules, also called spindles, that have the ability to
assemble and disassemble quicky. This network of rigid
micro-tubules inside the cell gives it shape, structure and also
has the ability to transfer organelles and various molecules to
different parts within the cell, functioning like a railway
system. But its most vital function is cell division.
You will easily understand the role of spindles by viewing this
short animation.
Here is a video of the micro-tubules, showing how they assemble
and dis-assemble. This is quite an amazing design and reminds us
of the complexity of life.
Mebendazole is known to interfere and inhibit the assembly of
the spindles, thus preventing the ability of the cells to
divide. The cell eventually dies of old age or aptosis.
Mebendazole is highly selective and somehow targets only
cancerous cells (as well as a host of intestinal parasites). At
the end of this article I will post a few of the many scientific
papers acknowledging these facts.
You will also see why there is virtually no pharmaceutical
interest in mebendazole. The big pharmaceutical companies are
promoting more toxic chemotherapy drugs because there is no
profit margin in mebendazole. It's yet another example of
corporate profit outweighing human benefits.
What is Cancer?
When a cell divides, the common notion is that the two resulting
cells are exactly identical. This is not correct. The process of
copying DNA is not perfect and there are usually errors,
although these are typically not serious. In fact, if a cell has
too many errors in its DNA code it will not be able to reproduce
and the errors die with that cell.
Human cells have a maximum number of times that they can
reproduce themselves before the accumulated errors finally
prevent reproduction -- it's called the Hayflick Limit. Most
scientists agree that this number is around 60 times.
This "programmed" lifespan of a cell is determined by the length
of a benign string of molecules attached to the ends of the DNA
coils. Like leaders on a movie film, these break off or become
misaligned during the replication process and provide a buffer
zone, protecting the real DNA code. The longer a cell's leader,
called a telomere, the more it can reproduce and the longer an
organism can live.
Biologists have found that cancer cells are cells in which the
damaged DNA code results in the activation of the telomere,
causing it to regrow. The hayflick limit becomes infinite. The
mutation makes the cell essentially immortal! Cancer does its
damage by outliving and outnumbering the normal cells.
The fight against cancer has been one of isolation and
selectively poisoning the cells. When cancer cells have
integrated themselves in vital tissues, this becomes a major
problem. Often, surgical attacks of cancerous tissue seems to
stimulate their growth even more, resulting in a temporary
relapse with regrowth. Likewise, chemotherapy and radiation are
not selective enough to protect healthy cells and their method
of death is toxic.
Mebendazole is different. It doesn't kill the cells with poison.
It specifically prevents the cell from reproducing.
What has Big Pharma done?
Mebendazole was first synthesized by Janssen Pharmaceutical
(later bought by Johnson & Johnson) in 1968. Its value as an
anti-worm medicine was recognized and by 1972 mebendazole was
being marketed under the name Vermox. Because the prescribed use
was eliminating parasites it was inexpensive and widely used.
The selective toxicity of mebendazole to cancerous cells had not
yet been discovered.
Back in 1960 the US Goverment declared war on cancer and funded
the Cancer Chemotherapy National Science Center. This agency
received over 1000 samples of chemicals -- mostly synthetic --
that were exposed to a variety of animal and human cancer cells.
It must have been like a scene from the movie, Andromeda Strain,
where thousands of substances were tested to kill the alien
virus brought back in an interstellar probe. With such large
sample numbers it was expected that some would prove effective
in killing tumors. And that's exactly what happened.
In 1964 a worker at a contractor for the Center thought to
include some natural chemistry in the study. He submitted a
resin from the bark of the Pacific Yew tree (Taxus brevifolia),
an endangered species endemic to the Washington State. It killed
tumor cells while not harming healthy cells. They called it
Taxol.
The down side to this discovery was that it took 12,000 pounds
of fresh Yew bark to make just 10 grams of Taxol! At first, no
pharmaceutical company was interested in developing the drug and
trials with human subjects were put off. Only in 1979, when
Taxol was shown to interfere with micro-tubules, did it receive
revived interest as a profitable anti-cancer medicine.
Same, Same, but Different
Researchers were discovering the value of microtubule inhibitors
in 1978. The safest one, mebendazole, was already on the market
as a treatment for worms, and it was cheap. For a pharmaceutical
company to invest in a cancer cure, it had to make a profit. So
the next best candidate was the resin in the Pacific Yew --
Taxol.
Taxol is a microtubule inhibitor... sort of. Rather than prevent
the tubules from forming, like mebendazole, Taxol acts like a
glue and prevents the tubules from disassembly. It's a process
called polymerization. This damages the internal structure of
the cell in ways not related only to cell division. The
side-effects of Taxol are many, while mebendazole has a
reputation for being harmless and well tolerated.
But there's another big difference between Taxol and mebendazole
-- the price. Taxol costs more than $200 a dose compared with
the $2 for some chewable Vermox pills.
A prophylaxis agent?
Before I list the studies, I could not help but wonder why a
person wouldn't take mebendazole periodically in one's life to
purge the body of cancerous cells. It is known to be well
tolerated with little toxicity. In some of the studies I will
quote, mebendazole was taken with Tagamet(TM) to reduce the
metabolizing effects of the liver and increase blood levels.
This would appear to be an idea that ought to be explored.
Mebendazole is not currently recognized as an anti-cancer drug.
The lack of investment by Big Pharma in conducting the many
trials and protocols will likely not change this status. But
physicians are capable of prescribing the medicine at their own
discretion. And ordinary people should be able to secure this
medicine themselves.
As promised -- here are some references for further research of
mebendazole:
The Anthelmintic Drug Mebendazole
Induces Mitotic Arrest and Apoptosis by Depolymerizing Tubulin
in Non-Small Cell Lung Cancer Cells, Ji-ichiro
Sasaki,Rajagopal Ramesh,Sunil Chada,Yoshihito Gomyo,Jack A.
Roth andTapas Mukhopadhyay, Molecular Cancer Therapy November
2002 1; 1201
"... Oral administration of MZ in mice elicited a strong
antitumor effect in a s.c. model and reduced lung colonies in
experimentally induced lung metastasis without any toxicity when
compared with paclitaxel-treated mice. [emphasis added] We
speculate that tumor cells may be defective in one mitotic
checkpoint function and sensitive to the spindle inhibitor MZ.
Abnormal spindle formation may be the key factor determining
whether a cell undergoes apoptosis, whereas strong microtubule
inhibitors elicit toxicity even in normal cells..."
Mebendazole Elicits a Potent
Antitumor Effect on Human Cancer Cell Lines Both in Vitro and
in Vivo, Tapas Mukhopadhyay,Ji-ichiro Sasaki,Rajagopal Ramesh,
and Jack A. Roth, Clinical Cancer Research September 2002 8;
2963
"We have found that mebendazole (MZ), a derivative of
benzimidazole, induces a dose- and time-dependent apoptotic
response in human lung cancer cell lines. In this study, MZ
arrested cells at the G2-M phase before the onset of apoptosis,
as detected by using fluorescence-activated cell sorter
analysis. MZ treatment also resulted in mitochondrial cytochrome
c release, followed by apoptotic cell death. Additionally, MZ
appeared to be a potent inhibitor of tumor cell growth with
little toxicity to normal WI38 and human umbilical vein
endothelial cells. When administered p.o. to nu/nu mice, MZ
strongly inhibited the growth of human tumor xenografts and
significantly reduced the number and size of tumors in an
experimental model of lung metastasis. In assessing
angiogenesis, we found significantly reduced vessel densities in
MZ-treated mice compared with those in control mice. These
results suggest that MZ is effective in the treatment of cancer
and other angiogenesis-dependent diseases..."
Mebendazole Induces Apoptosis via
Bcl-2 Inactivation in Chemoresistant Melanoma Cells, Nicole
Doudican, Adrianna Rodriguez, Iman Osman and Seth J. Orlow,
Molecular Cancer Research, August 2008 6; 1308
"...Our results suggest that this screening approach is useful
for identifying agents that show promise in the treatment of
even chemoresistant melanoma and identifies mebendazole as a
potent, melanoma-specific cytotoxic agent..."
Mebendazole inhibits growth of
human adrenocortical carcinoma cell lines implanted in nude
mice, Daniele Martarelli, Pierluigi Pompei, Caterina Baldi and
Giovanni Mazzoni, Cancer Chemotherapy and Pharmacology, Volume
61, Number 5, 809-817
"Adrenocortical carcinoma is a rare tumor of the adrenal gland
which requires new therapeutic approaches as its early diagnosis
is difficult and prognosis poor despite therapies used.
Recently, mebendazole has been proved to be effective against
different cancers. The aim of our study was to evaluate whether
mebendazole may result therapeutically useful in the treatment
of human adrenocortical carcinoma. We analyzed the effect of
mebendazole on human adrenocortical carcinoma cells in vitro and
after implantation in nude mice. In order to clarify mechanisms
of mebendazole action, metastases formation, apoptosis and
angiogenesis were also investigated. Mebendazole significantly
inhibited cancer cells growth, both in vitro and in vivo, the
effects being due to the induction of apoptosis. Moreover,
mebendazole inhibited invasion and migration of cancer cells in
vitro, and metastases formation in vivo. Overall, these data
suggest that treatment with mebendazole, also in combination
with standard therapies, could provide a new protocol for the
inhibition of adrenocortical carcinoma growth..."
Mebendazole Monotherapy and
Long-Term Disease Control in Metastatic Adrenocortical
Carcinoma, Irina Y. Dobrosotskaya, MD, PhD, Gary D. Hammer,
MD, David E. Schteingart, MD, Katherine E. Maturen, MD,
Francis P. Worden, MD, Endocrine Practice, Volume 17, Number 3
/ May-June 2011
"...A 48-year-old man with adrenocortical carcinoma had disease
progression with systemic therapies including mitotane,
5-fluorouracil, streptozotocin, bevacizumab, and external beam
radiation therapy. Treatment with all chemotherapeutic drugs was
ceased, and he was prescribed mebendazole, 100 mg twice daily,
as a single agent. His metastases initially regressed and
subsequently remained stable. While receiving mebendazole as a
sole treatment for 19 months, his disease remained stable. He
did not experience any clinically significant adverse effects,
and his quality of life was satisfactory. His disease
subsequently progressed after 24 months of mebendazole
monotherapy. Conclusion: Mebendazole may achieve long-term
disease control of metastatic adrenocortical carcinoma. It is
well tolerated and the associated adverse effects are minor...."
Antiparasitic mebendazole shows
survival benefit in 2 preclinical models of glioblastoma
multiforme, Ren-Yuan Bai, Verena Staedtke, Colette M. Aprhys,
Gary L. Gallia and Gregory J. Riggins, Neuro Oncology, (2011)
13(9): 974-982
"...mebendazole significantly extended mean survival up to 63%
in syngeneic and xenograft orthotopic mouse glioma models.
Mebendazole has been approved by the US Food and Drug
Administration for parasitic infections, has a long track-record
of safe human use, and was effective in our animal models with
doses documented as safe in humans. Our findings indicate that
mebendazole is a possible novel anti-brain tumor therapeutic
that could be further tested in clinical trials...
I'd like to hear from anyone with experience or additional
information on this drug.
Epilogue: Discontinuation in United
States
The last manufacturer of mebendazole in the United States, Teva
Pharmaceuticals, announced on October 7, 2011, that they have
ceased manufacture of this product. As of December, 2011, it is
no longer available from any manufacturer in the USA. No reason
was given for this discontinuation, but it's blatantly obvious.
VERMOX
Active substance: Mebendazole
6 Tablets 100mg
Pharmacological effects:
Brand Vermox is an antihelminthic drug with a broad action
spectrum. Vermox is highly effective for enterobiasis and
trichocephaliasis treatment. Vermox works by interfering with
the glucose utilization in the helminth's tissue. Vermox also
helps to inhibit the synthesis of tubulin and slow down the
production of ATP.
Indications: Brand Vermox is
used for the treatment of the following diseases:
* Enterobiasis
* Ascariasis
* Hookworm disease
* Strongyloidosis
* Trichocephaliasis
* Echinococcosis
* Various nematodes
* Alveococcosis disease
* Capillariasis
* Gnathostomosis
* Various helminth infection
Warnings and Precautions: The drug
should not be used in the following conditions:
* Hypersensitivity to any components of the preparations.
* Pregnancyand lactation period
* Child age (up to age of 2)
* Nonspecific ulcerative colitis
* Grohn's disease
* Liver decompensation
Vermox side effects:
Drugs may cause side-effects which in specific patients may
manifest differently. In the following paragraph we want to
underline the most serious and frequent side effect of Brand
Vermox that were identified by the drug manufacturers. The
possibility of the adverse effect manifestation depends only on
the individual and his specific traits. Mebendazole side effects
include:
* Dizziness, headaches, nausea, vomiting, stomachache, diarrhea
* Allergic reactions: skin rash, nettle rash, angioneurotic
edema,
* “Liver” transaminase activity increase
* Hypercreatinemia
* Leukopenia
* Anemia
* Eosinophilia
* Hair loss
* Erythrocyturia
* Negative influence on the fetation
For full information on any risks and adverse effects associated
with Vermox, please consult your doctor, read the included
leaflet or contact our customer support service.
Interactions: Before using Vermox please tell your doctor which
drugs or supplements you are already taking including those
bought without a prescription. Also check if any additional
medicine which you will take during the course of Mebendazole
therapy are safe in combination. Especially mention if you are
taking the following groups of drugs:
* Insulin
* Lipophilic substances
* H2-histamine receptors blocker
* Anticonvulsants
Patients information:
Mebendazole is not to be shared with healthy individuals. It is
strictly FORBIDDEN to use the drugs in treatment of any
conditions unrelated to their indications. The product as well
as utilized vials, syringes, needles if used during the
course of treatment should be kept out of reach of children and
never reused.
Dosage:
Orally pills.
Enterobiasis - adults and adolescents, 100 mg, children 2-10
years - 25-50 mg dose, and again after 2-4 weeks in the same
doses.
Ascariasis, trichuriasis, hookworm disease, taeniasis,
strongyloidiasis and mixed helminthiasis - 100 mg in the morning
and evening for three days.
Trichinosis - 200-400 mg 3 times daily for 3 days, and from 4 th
to 10 th - 400-500 mg 3 times a day.
Echinococcosis - 500 mg two times a day the first 3 days and 3
times a day over the next 3 days. Later appointed to 25-30 mg /
kg per day in 3-4 doses.
J
Pharm Sci. 97(1):542-52 (Jan. 2008)
Synthesis and characterization of a
new mebendazole salt: mebendazole hydrochloride.
Brusau EV, Camí GE, Narda GE, Cuffini S, Ayala AP, Ellena J.
Química Inorgánica, Departamento de Química, Facultad de
Química, Bioquímica y Farmacia, Universidad Nacional de San
Luis, Chacabuco y Pedernera, 5700 San Luis, Argentina.
Abstract
Mebendazole hydrochloride
[(5-benzoyl-1H-benzimidazole-2-yl)-carbamic acid methyl ester
hydrochloride, MBZ.HCl], a new stable salt of mebendazole (MBZ),
has been synthesized and characterized. It can easily be
obtained from recrystallization of forms A, B, or C of MBZ in
diverse solvents with the addition of hydrochloric acid
solution. Crystallographic data reveals that the particular
conformation adopted by the carbamic group contributes to the
stability of the network. The crystal packing is stabilized by
the presence of three N-H...Cl intermolecular interactions that
form chains along the b axis. The XRD analyses of the three
crystalline habits found in the crystallization process
(square-based pyramids, pseudohexagonal plates, and prismatic)
show equivalent diffraction patterns. The vibrational behavior
is consistent with crystal structure. The most important
functional groups show shifts to lower or higher frequencies in
relation to the MBZ polymorphs. The thermal study on MBZ.HCl
indicates that the compound is stable up to 160 degrees C
approximately. Decomposition occurs in four steps. In the first
step the HCl group is eliminated, and after that the remaining
MBZ polymorph A decomposes in three steps, as happens with
polymorphs B and C.
Synthesis
Parasitology
Today 6(4):107 (1990); The Synthesis & Chemistry
of Certain Anthelmintic Benzimidazoles ( PDF )
Sciencedirect.com
Bioorganic
&
Medicinal Chem. 11:4615-4622 (2003); Synth. &
Antiparasitic Activity of Albendazole & Mebendazole
Derivatives ( PDF
)