Cancer cell 'executioner' found ~ synthetic molecule which caused cancer cells to self-destruct.

BBC ^ | Sunday, 27 August 2006, 23:51 GMT 00:51 UK | BBC staff

[Ernest_at_the_Beach]

Cancer cell 'executioner' found

Cancer cells keep dividing because the cell suicide process fails

Scientists have developed a way of "executing" cancer cells.

Healthy cells have a built-in process which means they commit suicide if something is wrong, a process which fails in cancer cells.

The University of Illinois team created a synthetic molecule which caused cancer cells to self-destruct.

Cancer experts said the study, in Nature Chemical Biology, offered "exciting possibilities" for new ways of treating the disease.

These findings present an exciting new therapeutic strategy for the treatment of some cancers Dr Michael Olsen, Cancer Research UK

One of the hallmarks of cancer cells is their resistance to the body's cell suicide signals, which allow them to survive and develop into tumours.

All cells contain a protein called procaspase-3, which the body should be able to turn into caspase-3 - an executioner enzyme.

But this transformation does not happen in cancer cells, even though certain types, such as colon cancer, leukaemia, skin and liver cancers paradoxically have very high levels of procaspase-3.

Healthy cells unaffected

The researchers examined more than 20,000 structurally different synthetic compounds to see if any could trigger procaspase-3 to develop into caspase-3.

They found the molecule PAC-1 did trigger the transformation, and cancer cells from mice and from human tumours could be prompted to self-destruct - a process called apoptosis.

The more procaspase-3 a cancer cell had, the less of the molecule was needed.

Healthy cells, such as white blood cells, were found to be significantly less affected by the addition of PAC-1 because they had much lower levels of procaspase-3, so cell-suicide could not be triggered.

When the scientists tested PAC-1 on cancerous and non-cancerous tissue from the same person, the tumour cells were 2,000-fold more sensitive to PAC-1.

Since different levels of procaspase-3 were found in the cell lines studied, the researchers suggest some patients would be more responsive to this therapy than others, so the it might one day be possible to tailor treatments to individual patients.

'Exciting'

Professor Paul Hergenrother, who led the research, said: "This is the first in what could be a host of organic compounds with the ability to directly activate executioner enzymes.

"The potential effectiveness of compounds such as PAC-1 could be predicted in advance, and patients could be selected for treatment based on the amount of procaspase-3 found in their tumour cells."

Cancer Research UK expert Dr Michael Olson, who is based at the Beatson Institute for Cancer Research in Glasgow, said: "These findings present an exciting new therapeutic strategy for the treatment of some cancers.

"It remains to be seen which, if any tumour types consistently express elevated procaspase-3. That will tell us how many patients could potentially benefit from the drug.

"Clinical trials will be needed to confirm whether procaspase-3 causes any adverse effects in humans."

[Crazieman]

Wow...

[Ernest_at_the_Beach]

Man this would be some good news if this progresses....the money should flow for this research....

[SittinYonder]

It seems like I read frequently that some new something-or-other has been discovered which cures/reverses cancer, and then I never hear of it again. This is the second time I've seen an article about this, so maybe there's something to it.

[Fiddlstix]

BTTT

[spanalot]

Smoke em if you got em!

[Smokin' Joe]

the money should flow for this research....

This is the sort of research all that 'anti-tobacco jihad' money should have been spent on all along.

Cure the disease.

[Ernest_at_the_Beach]

There was a company that was promising at one time that had isolated a portion of aspirin that seemed to hold promise to cause apoptosis of the cancer cells...some of this may have been built on some of that work...

Company's name was Cell Pathways...I think....

Googling :

Cell Pathways scientists describe mechanism by which SAANDS compounds trigger programmed death in cancerous and precancerous cells

*************************************AN EXCERPT **********************************

New drug target for inducing apoptosis in abnormal cells published in Cancer Research

HORSHAM, PA (July 5, 2000) -- Scientists at Cell Pathways, Inc. (Nasdaq: CLPA) and their collaborators have identified a new drug target that may play a key role in cancer cell survival. Exisulind (Aptosyn™) and other compounds in the company's family of selective apoptotic antineoplastic drugs (SAANDs) inhibit this target, cyclic GMP phosphodiesterases of the PDE5 and PDE2 gene families that have been found to be over-expressed in cancerous and precancerous cells of the colon. The inhibition of these target proteins triggers a chain of events which results in the programmed cell death, or apoptosis, of cancerous and precancerous cells, but not normal ones. The drugs have additionally been shown to inhibit the growth of a broad variety of malignant tumor cells beyond colon tumors, in both cell culture and animal models of human cancers.

The new research appears in the July 1 issue of the journal Cancer Research. Cell Pathways scientists and their collaborators at the University of South Alabama College of Medicine, and the University of Colorado authored the paper.

Apoptosis and SAANDs

Apoptosis is the body's response to a normal, orderly sequence of biochemical or physical signals by which damaged or "worn out" cells are eliminated to make way for healthy, new cells. When the mechanism of apoptosis goes awry, cells continue to multiply and grow inappropriately, forming a mass of tissue -- a cancerous tumor. In colon cancer, excessive cell growth occurs as the result of the accumulation of a regulatory protein, beta-catenin, caused by mutations in the adenomatous polyposis coli (APC) gene.

The researchers showed that exisulind and other SAANDs induce apoptosis in colon tumor cells by inhibiting the different forms of cGMP PDE in these cell lines. This results in a sustained increase in cGMP in the cells and the induction of cGMP-dependent protein kinase G (PKG). This rise in PKG activity causes beta-catenin to be degraded in neoplastic cells, thus triggering cell death by apoptosis through well-studied mechanisms. In addition, SAANDs that are better inhibitors of PDE5 and PDE2 than exisulind also show parallel increases in ability to induce

[Ernest_at_the_Beach]

See post #8.

[Centurion2000]

wow .... that's medical articles bookmarked today. Did you see the one on using your own adult stem cells to rejuvenate heart tissue?

[Moonman62]

This is the sort of research all that 'anti-tobacco jihad' money should have been spent on all along. Cure the disease.

That sounds just like the AIDS crowd.

[Smokin' Joe]

That sounds just like the AIDS crowd.

How so?

Cancer was around before tobacco use, and will continue to be around if you could make all tobacco dissappear today, this instant.

Cure the disease, and everyone benefits, tobacco user or not.

This ain't bungholing, it's an F'n cigarette. SHeesh!

Or would you argue a few billion more dollars should be pissed down the endless computer model research rathole to tell us all cigarettes are bad for you?

[SteveMcKing]

"That sounds just like the AIDS crowd."

I wonder if gay men are addicted to sex like smokers can't stop puffing. Needle-drug users are certainly gonzo from reality.

Anyway, it took generations before people knew about smoking hazards. AIDS was identified in a very short time by comparison. Practically nobody after the late 1980s can blame anyone but themselves if they've acquired it.

That is sad, tragic, and stupid.

[aruanan]

"Clinical trials will be needed to confirm whether procaspase-3 causes any adverse effects in humans

More old humans will live longer, putting additional strains on Social Security and the planet's resources? < / sarcasm >

[SteveMcKing]

Actually the same can be said of those who started smoking, probably since the '70s.

[Dustbunny]

Great!! Hopefully this is a giant step forward in ending cancer.

[Mad_Tom_Rackham]

God bless.

[AFPhys]

This sounds like one tremendously promising approach to killing cancerous cells!

[Moonman62]

Cancer was around before tobacco use, and will continue to be around if you could make all tobacco dissappear today, this instant.

Cure the disease, and everyone benefits, tobacco user or not.

Then there was no need to bring up tobacco.

The AIDS crowd didn't want to change their behavior, they wanted a cure instead.

[My Favorite Headache]

Sadly your sarcasm is a reality in the world of the government..hence why this will probably not see the light of day.