Cell's 'biological clock' may be key to cancer cure

UT Southwestern Medical Center researchers found that a small molecule 6-thio-2'-deoxyguanosine could stop the growth of cancer cells in culture and decrease the growth of tumors in mice, and have targeted telomeres with 6-thiodG, that takes advantage of the cell's 'biological clock' to kill cancer cells and shrink tumor growth.

Dr. Jerry W. Shay, Professor and Vice Chairman of Cell Biology at UT Southwestern, said that they observed broad efficacy against a range of cancer cell lines with very low concentrations of 6-thiodG, as well as tumor burden shrinkage in mice.

6-thiodG acts by targeting a unique mechanism that is thought to regulate how long cells can stay alive, a type of aging clock. This biological clock is defined by DNA structures known as telomeres, which cap the ends of the cell's chromosomes to protect them from damage, and which become shorter every time the cell divides. Once telomeres have shortened to a critical length, the cell can no longer divide and dies though a process known as apoptosis.

Cancer cells are protected from this death by an RNA protein complex called telomerase, which ensures that telomeres do not shorten with every division. Telomerase has therefore been the subject of intense research as a target for cancer therapy. Drugs that successfully block its action have been developed, but these drugs have to be administered for long periods of time to successfully trigger cell death and shrink tumors, leading to considerable toxicities. This outcome is partially because cells in any one tumor have chromosomes with different telomere lengths and any one cell's telomeres must be critically shortened to induce death.

6-thiodG is preferentially used as a substrate by telomerase and disrupts the normal way cells maintain telomere length. Because 6-thiodG is not normally used in telomeres, the presence of the compound acts as an 'alarm' signal that is recognized by the cell as damage. As a result, the cell stops dividing and dies.

Telomerase is an almost universal oncology target, yet there are few telomerase-directed therapies in human clinical trials, researchers noted.

Importantly, unlike many other telomerase-inhibiting compounds, the researchers did not observe serious side effects in the blood, liver and kidneys of the mice that were treated with 6-thiodG.
Dr. Shay said that they believe this small molecule would address an unmet cancer need in an underexplored area that would be rapidly applicable to the clinic.

The paper is published in the journal Cancer Discovery.

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Statins may slow aging process

Researchers have found that statins, a class of drugs widely used for lowering cholesterol, may also slow down the process of human ageing, according to a study.

Statins are commonly used to reduce the risk of heart attack and stroke in patients who are at high risk. They work by blocking the action of an enzyme in the liver that is responsible for making cholesterol.

But now, researchers have discovered that statins could reduce the rate at which telomeres "shorten," meaning they could potentially be used as an anti-ageing therapy.

A telomere is an area of repetitive DNA at the end of a chromosome, protecting it from deterioration. As a person ages, telomeres are thought to shorten, limiting the number of cells which divide, therefore decreasing a person's lifespan.

For the study, the researchers conducted an experiment on 203 participants who were divided into two groups. One group was under chronic statin therapy, while the other group did not use statins. Telomerase activity was measured in both of the groups.

The findings showed that the participants who were undergoing statin therapy showed higher levels of telomerase activity in their white blood cells linked to lower levels of telomere shortening, compared with the group who did not use statins.

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