A small new molecule that can kill cancer cells and shrink tumour growth by targeting the ‘biological clock’ has been discovered.
Researchers at the University of Texas Southwestern Medical Centre in the US found that the molecule called 6-thiodG could stop the growth of cancer cells in culture and decrease the growth of tumours in mice.
“We observed broad efficacy against a range of cancer cell lines with very low concentrations of 6-thiodG, as well as tumour burden shrinkage in mice,” said Dr Jerry W Shay, Professor and Vice Chairman of Cell Biology at UT Southwestern.
6-thiodG acts by targeting a unique mechanism that is thought to regulate how long cells can stay alive, a type of ageing 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 through 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 tumours, leading to considerable toxicities.
This outcome is partially because cells in any one tumour 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 recognised by the cell as damage. As a result, the cell stops dividing and dies.
“Using telomerase to incorporate toxic products into telomeres is remarkably encouraging at this point,” said Wright.
“Since telomerase is expressed in almost all human cancers, this work represents a potentially innovative approach to targeting telomerase-expressing cancer cells with minimal side effects on normal cells,” said Shay.
The research appears in the journal Cancer Discovery.