Pancreatic cancer cells contain high levels of hydrogen peroxide
Reactive oxygen species (ROS) are reputed for their involvement in
carcinogenesis. Results from a study published in the journal Angewandte Chemie
have now shown that the level of one such ROS, hydrogen peroxide, is
significantly higher in pancreatic cancer cells, unlike the level of
other reactive oxygen species. This makes hydrogen peroxide an exciting
target for cancer research and treatment.
© Wiley-VCH, re-use with credit to 'Angewandte Chemie' and a link to the original article.
Reactive oxygen species play an important role in the functioning of
our cells. They are formed during cellular processes and can target and
modify cell building blocks such as lipids and other molecules. They are
usually kept in check by the cell to prevent them accumulating and
becoming too harmful. However, in cancer cells, this
up-and-down-regulation appears to be disrupted, making reactive oxygen
species a hot topic in cancer research.
Despite this intense interest, these tiny molecules are very
difficult to analyze due to being extremely short-lived. A team of
researchers led by Renato Zenobi of ETH Zurich, Switzerland, have now
been able to selectively measure the concentrations in cancer cells of
three prominent members of this group of compounds—hydrogen peroxide,
superoxide, and hydroxyl radicals. Using specific chemical reactions,
high-resolution mass spectrometry and biological assays, the team
detected the levels of the three species separately. They also showed
that hydrogen peroxide is significantly increased in pancreatic cancer
cells compared to other ROS molecules, and that this increased level
makes a critical contribution to the survival of cancer cells.
The study also showed that cancer-promoting mutations lead to
suppression of the genetic expression of enzymes that break down
hydrogen peroxide. Higher concentrations of hydrogen peroxide altered
the lipid composition of the cells. Because cancer cells divide very
quickly, they require huge amounts of lipids to form new membranes. The
team observed that suppression of the enzyme catalase, which breaks down
hydrogen peroxide, led to more lipids typical of cancer cell membranes.
The authors concluded that down-regulation of hydrogen peroxide is
disrupted in pancreatic cancer cells, which is why they were able to
detect more of this ROS. Because it was clearly only hydrogen peroxide,
and not the other reactive oxygen species, that was incorrectly
regulated, the team proposes differentiated detection of these molecules
in the future, rather than simply detecting reactive oxygen species as a
sum parameter. New analysis techniques, such as the team’s powerful
mass spectrometry method, make this distinction possible, they argue.
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About the Author
Renato Zenobi is
Professor of Analytical Chemistry at the Organic Chemistry Laboratory at
ETH Zurich, Switzerland. The Zenobi team designs and applies a range of
mass spectrometry and nanoscale imaging techniques for the rapid and
sensitive analysis of biomolecules and biochemicals as well as surfaces.
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