Biological clocks in cells could be utilized to detect and treat some forms of cancer, new research reveals.
University of Texas Southwestern Medical Center biologists have found they can use a chemical called 6-thio-2'-deoxyguanosine (6-thiodG) to target telomeres in cells. These are strands of genetic material at the tips of DNA strands that protect the structures like plastic tips on the end of shoelaces.
Researchers found the introduction of 6-thiodG to tumors significantly reduced the growth of cancer cells in mice examined in a study.
"We 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," Jerry Shay, associate director of the Harold C. Simmons Comprehensive Cancer Center, said.
Cells reproduce through division, and each time a cell divides, telomeres become shorter, providing less protection against damage. Once these structures reach a certain length, they can no longer go through the process of division, and cellular death, or apoptosis, takes place. Cancer cells do not undergo this cellular death, making this class of diseases especially difficult to treat.
"It is now evident that the progressive loss of the telomeric ends of chromosomes is an important timing mechanism in human cellular aging. Human telomeres contain long stretches of the repetitive sequence TTAGGG which are bound by specific proteins," Shay and others wrote in Telomerase and cancer, published by Oxford Journals.
Telomerase is an enzyme which acts to protect telomere strands from becoming shorter, thereby protecting the DNA strand from becoming damaged. Medical researchers have spent years developing new cancer treatments that would inhibit the action of telomerase, allowing the dangerous cells to die out naturally. However, these drugs need to be administered in large doses, over significant periods of time, which can lead to significant toxic effects on livers and kidneys of patients, as well as leading to problems in blood chemistry.
Telomerase, based on 6-thiodG, alters actions regulating how telomere length is maintained. The presence of the enzyme alerts the cell it is damaged, and cellular death ensues.
Mice treated with 6-thio-2'-deoxyguanosine experienced few adverse side effects or health problems, researchers noted.
Cancer cells which are telomerase-positive (so-called "immortal cells") exposed to 6-thiodG underwent "telomere uncapping," leading to cellular death, while normal cells were unaffected.
"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," Shay told the press.
Discovery of the link between 6-thiodG and telomeres was published in the journal Cancer Discovery.