Living organisms experience various stresses during their lifespans. These stresses include radiation, ultraviolet rays, and chemical substances which directly damage DNA and cause cancer. Organisms are able to speedily repair DNA when it is damaged, however, when the damage is severe they manifest two different cell responses. These are apoptosis, a type of controlled cell death, and cellular senescence, which permanently suspends cell growth. It has been suggested that by secreting various proteins, senescent cells may accelerate the proliferation and malignant transformation of surrounding cancer cells. Now, a study from researchers led by the Kobe University identifies genes that control cellular senescence. The team state that by developing drugs that suppress the activity of these genes, their discovery has potential applications for creating new highly-effective anticancer drugs, or use in anti-aging drugs. The opensource study is published in the journal Scientific Reports.
Previous studies show that cancer treatment based on radiation and anticancer drugs aims to destroy cancer tissue by triggering apoptosis in cancerous cells. One of the changes in cancerous cells caused by this treatment is the appearance of senescent cells. Earlier studies from the lab showed that cell senescence was effectively induced by using low concentrations of anticancer drugs on cancerous cells. The group found that if cancerous cells are treated with a low concentration of the anticancer drug etoposide this induces cell senescence, and if they are treated with a high concentration of the drug this induces apoptosis. The current study distinguishes genes specific for senescence from those that universally respond to DNA damage, and provides evidence that some of the identified genes are functionally involved in the senescence program.
The current study treated cancerous cells under three different conditions, namely with no etoposide, or with a low dose of etoposide, or using a high dose of etoposide. They then used DNA microarrays to identify the genes where a rise in transcription levels could be observed.
Results show 126 genes where three times as much expression was recorded with a low dose of etoposide compared to no etoposide, and 25 genes that showed twice as much expression with a low dose of etoposide compared with a high dose of etoposide. Data findings show that these 25 genes are expected to express specifically in senescent cells since the other factors caused by DNA damage are removed, and researchers confirmed that the genes involved in causing cell senescence were among them.
The team surmise that their study identifies the genes which are functionally involved in the senescence program. They go on to add that if a drug can be developed which targets and regulates the activity of the genes controlling senescence identified in this research, the global medical community can limit the emergence of senescent cells and potentially increase the effectiveness of cancer treatment. For the future, the researchers state that drugs which control cell senescence could have potentially benefits for the development of anti-aging products.