Mechanism through which cyclooxygenase-2 enzymes promote development of colon cancer is discovered
The molecular interactions that allow
cyclooxygenase-2 enzymes to promote development of colon cancer
have been discovered, according to an article published online on
June 30th by the Proceedings of the National Academy of Sciences.
In laboratory studies involving human and
rat cells, the investigators defined the multiple steps initiated
by the family of enzymes, including prominent roles for cyclic adenosine
monophosphate and proteins called inhibitors of apoptosis. The result
of the molecular interactions is suppression of apoptosis, resulting
in uncontrolled cell growth and eventually colon cancer.
Specifically, apoptosis is a result of balanced
molecular actions taking place at 2 different starting points. An
extrinsic pathway, also called the death receptor pathway, activates
1 set of molecules. A second, intrinsic pathway is mediated by mitochondria.
As the 2 pathways meet and join they cause chemical reactions down
a final pathway that result in cell death. The proteins termed inhibitors
of apoptosis act at the point where the 2 pathways merge.
The chain of events begins with enzyme-induced
increases in formation of prostaglandins, and prostaglandin-induced
increases in formation of cyclic adenosine monophosphate. Cyclic
adenosine monophosphate is the molecule that actually blocks normal
cell death through activation of inhibitors of apoptosis.
According to Paul Insel, MD, senior author
of the study, the findings may have implications for understanding
the origins of other cancers in which cyclooxygenase-2 or similar
enzyme activity appear to play a role, including certain lung cancers,
prostate cancer, squamous cell carcinomas of the head and neck,
and some types of breast cancer.
In addition, by pinpointing each step in
the molecular chain of events initiated by cyclooxygenase-2 enzymes,
the study offers potential new targets for drug therapies that have
greater effectiveness and fewer side effects than those associated
with nonsteroidal anti-inflammatory agents. Long-term use of these
agents is associated with a 40 to 50 percent decrease in the incidence
of colon cancers.
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