( s disease and ulcerative colitis bowel...)Gut research yields new anti-cancer approach

s disease and ulcerative colitis, bowel diseases that cause pain and diarrhea. Specifically, they were comparing the effect on inflammation of encouraging the action of the PPARgamma protein (with activator compounds) against discouraging it (with inhibitors). The team conducted these experiments using colorectal cancer cells as study models because they arise from normal gut cells and share some of their qualities (e.g. normal inflammatory signals). Unlike normal gut cells, however, cancer cells do not die when removed from the gut wall. Living on in the absence of normal survival signals makes cancer cells dangerous in the body, but useful as cell lines for study.

While comparing PPARgamma activators and inhibitors, Schaefer noted with frustration that her cancer cells were dying before she could complete her experiments. Retracing her steps, she found that she had used too much inhibitor. The team, led by Lawrence J. Saubermann, M.D., associate professor of Medicine at the Medical Center, realized they had come across a potentially new therapeutic effect, and launched experiments to confirm it.

Study Details

In the newly published study, researchers observed the effects of three compounds known from the literature to inhibit PPARgamma, T0070907, GW9662 and BADGE, on the ability of colorectal tumor cells to survive. High doses (10-100 ìM) of all three interfered with colorectal cancer cell growth, reduced the cells' ability to spread through the bloodstream to cause new tumors elsewhere (metastasize) and caused cells to self-destruct, generally within 24 hours. Further experiments showed that high-dose PPARgamma inhibition destroyed cancer cell microtubules, protein structures that form part of the skeleton of cells.

Beyond providing structural support and shape to cells, microtubules expand and shrink to generate the force needed for cells to divide, a basic process in tumor growth. Microtubules are made of two rel
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Source:University of Rochester Medical Center

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