Snake venom may hold key for heart disease, cancer cure

Japanese scientists have claimed that a number of toxins found in snake venom could help develop new therapies for chronic diseases like heart attack, stroke and cancer.

Washington: Japanese scientists have claimed that a number of toxins found in snake venom could help develop new therapies for chronic diseases like heart attack, stroke and cancer.

The scientists, who reported their findings in the
Journal of Biological Chemistry, said that inhibiting a
protein found on the surface of blood cells known as platelets
may combat both irregular blood clotting and the spread of
certain cancers throughout the body.

"The finding that platelets not only play a role in blood
clotting but also in the development of vessels that allow
tumours to flourish was quite unexpected and paves the way for
new research on the role or roles of platelets," said Katsue
Suzuki-Inoue, the associate professor at the University of

She said: "When a blood clot, or thrombus, forms during
the body`s normal repair process, it`s doing its job. But,
thrombotic diseases, such as heart attack and stroke, are
leading causes of death in developed countries."

"Understanding and manipulating the underlying chemical
reactions could help us save many lives."

The researchers said that snake venom contains a vast
number of toxins that target proteins in platelets.

"Some of those toxins prevent platelets from clotting,
which can lead to profuse bleeding in snake bite victims.

Others potently activate platelets, which results in blood
clots," said Yonchol Shin, an associate professor at Kogakuin
University who specialises in snake toxins.

"Identification of the molecular targets of many of these
toxins has made an enormous contribution to our understanding
of platelet activation and related diseases."

In 2000, researchers had come across a protein on the
surface of platelets, called CLEC-2. At the time, it remained
unclear how CLEC-2 was produced or what its job was, but the
team suspected it was worth further study.

In 2006, the team discovered how rhodocytin -- a molecule
purified from the venom of the Southeast Asia pit viper
Calloselasma rhodastoma -- binds to the CLEC-2 receptor
protein on the platelet surface, spurring the platelet to clot
with others like it.

Then, in 2007, Suzuki-Inoue and her colleagues reported
how a separate molecule, called podoplanin, binds to the
CLEC-2 platelet receptor protein very much like the venom
molecule does.

"To shield themselves from the immune system, cancer
cells send out a chemical, podoplanin, which binds to the
CLEC-2 receptor protein on platelets, telling the platelets to
get together and form a protective barrier around the cancer
cells," Suzuki-Inoue explained.

"Once enveloped, the cancer cells are not detected by the
immune system and are able to bind to blood vessels` inner
linings and spread, or metastasise, throughout the body."

Using a mouse model, the team in 2008 showed that
blocking the tumour protein podoplanin from binding with the
platelet receptor protein CLEC-2 could prevent tumours from
metastasising to the lung.

The recent investigations by the team hinged on the
generation and study of genetically engineered mouse embryos
that lacked the platelet receptor protein CLEC-2.

In the end, the experiments showed that CLEC-2 is not
only necessary for blood clotting but also necessary for the
development of a different type of vessel, specifically
lymphatic vessels that carry fluid away from tissues and
prevent swelling, or edema.

It has been known that tumours generate blood vessels to
promote their growth, and the scientists found that
interaction between the platelet`s CLEC-2 protein and the
podoplanin molecule in lymphatic cells plays an essential role
in this process.

"If this is the case, a drug that blocks that interaction
would prevent the spread of tumours through lymphatic
vessels," the researchers said.