Spermine Oxidase, Hydrogen Peroxide, Inflammation, and Prostate Cancer

Imagine looking for the first dominos, after a whole line has fallen — retracing the steps of a chain reaction to find the root cause — and you’ll have a pretty good idea what molecular pharmacologist Robert Casero, Ph.D., is trying to do. Actually, this is what many Brady researchers are trying to do; but in Casero’s case, the particular series of events involves an oxidized molecule called spermine.

His starting platform is pioneering Brady research, well under way in many labs here, showing that inflammation plays a key role in the development of prostate cancer. Inflammation causes oxidative damage — harm to DNA, which can cause one or more genes to mutate — and this, in turn, can lead to cancer. One substance known to cause oxidative damage is hydrogen peroxide, which is produced when there is inflammation. The same stuff that, in a bottle in your medicine cabinet, kills germs can also hurt your cells. It doesn’t take much — very tiny amounts, even just one molecule’s worth, can cause harm.

Casero, the Irene and Bernard L. Schwartz Scholar, has taken this process back a step further. What, in inflammation, causes hydrogen peroxide to be made? This can happen when an enzyme called spermine oxidase mixes oxygen with spermine, a substance found in high concentrations in the prostate. Previously, Casero and colleagues found that when there is inflammation in the stomach (caused by bacterial infection with H. pylori) spermine oxidase makes hydrogen peroxide, and damages DNA. Casero suspected that this also happens in the prostate — which has the highest concentration of spermine of any human tissue.

The same stuff that, in a bottle
in your medicine cabinet, kills
germs can also hurt your cells.

As he and colleagues have pursued this, they have built up an incriminating file showing that inflammation — and inflammatory cytokines (regulatory proteins, released by the immune system) — causes more spermine oxidase to be made. “Our data indicate that increased spermine oxidase is associated with prostate cancer,” he says. “As the product of spermine oxidase is hydrogen peroxide, we suspect that this can lead to greater DNA damage, and ultimately, to the initiation and progression of prostate cancer.” Are men with higher levels of spermine oxidase more prone to developing prostate cancer? Do men who don’t have prostate cancer have lower levels of spermine oxidase? These are among the next questions Casero plans to pursue.

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