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University of Pittsburgh researchers have found that aspirin aids in switching on a death signal for cancer cells and could be used to prevent many aggressive secondary cancers. In a study published in the December 9 issue of the Journal of Biological Chemistry, Pitt researchers report that aspirin, combined with a promising new cancer therapy known as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), can induce cancer cells previously resistant to TRAIL therapy to self-destruct. The investigators say that if these findings hold up in larger studies, aspirin could become a routine therapy for helping to prevent the recurrence of many aggressive cancers, such as breast, prostate, and colon cancers.
"When cancers recur after initial therapy, they tend to be extremely aggressive, and patient prognosis is poor," said Yong J. Lee, a professor in the departments of surgery and pharmacology at the University of Pittsburgh School of Medicine and lead author of the study. "If we could find ways to prevent these secondary cancers from occurring, we could save many lives. Aspirin is a low-cost medicine that, in our studies, appears to have great potential for helping to prevent such cancer recurrences."
TRAIL is a protein that is expressed by cells of the immune system. Studies have shown that TRAIL induces programmed cell death--or apoptosis--in cancer cells while having little or no effect in normal healthy cells. Apoptosis is one of several mechanisms by which damaged cells self-destruct and is the body's way of ensuring that only healthy cells reproduce. Because cancer cells have lost their ability to undergo apoptosis, they continue to reproduce and spread throughout the body.
TRAIL has been shown in cell cultures and animal models to induce cancer cell apoptosis, both alone and in combination with other drugs. Some studies have found, however, that not all cancers are sensitive to TRAIL. In fact, many tumor cells are completely resistant to TRAIL's effects, creating an intensive search for compounds that can overcome this resistance.
Based on other studies showing that aspirin can prevent the formation of tumors caused by ultraviolet radiation and carcinogens, Lee and his colleagues decided to test the ability of aspirin to increase the sensitivity of TRAIL-resistant cancer cells to apoptosis. Cells treated with either aspirin or TRAIL alone showed little or no cell death. However, pretreatment of the TRAIL-resistant cancer cells with aspirin promoted cell death when TRAIL was added. A more detailed analysis suggests that TRAIL induces apoptosis via cellular mitochondria.
Lee and his colleagues believe these findings could soon be applied in the clinical setting and result in the increased effectiveness of TRAIL for treating a number of aggressive cancers, particularly those that overexpress a key gene that makes the cancer cells difficult to treat. (Advocate.com)