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.
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
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
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)
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