Molecule Fights Cancer by Activating Tumor Suppressor

Promising treatment inhibits interaction of tumor suppressor and inhibitor, reducing tumors in mice

MONDAY, March 10 (HealthDay News) -- A molecule dubbed MI-219, which inhibits the interaction between tumor suppressor p53 and its primary cellular inhibitor MDM2, shows promise as a new anticancer agent, according to research published online March 3 in the Proceedings of the National Academy of Sciences.

Sanjeev Shangary, Ph.D., of the University of Michigan in Ann Arbor, and colleagues found that MI-219 induces cell cycle arrest in cancerous and normal cells with wild-type p53; however, although it is effective in inducing apoptosis in cancer cells with wild-type p53, it has minimal effect on normal cells.

The researchers report that the molecule inhibited tumor growth by 75 percent in a SJSA-1 xenograft mouse model after 14 days, and reduced LNCaP tumor size from 184 mm3 to 134 mm3 after 17 days. The mice didn't demonstrate signs of toxicity. In addition, the molecule activated p53 in normal tissues with minimal accumulation, the report indicates.

"MI-219 stimulates rapid but transient p53 activation in xenograft tumor tissues, resulting in inhibition of cell proliferation, induction of apoptosis, and complete tumor growth inhibition consistent with the notion that established tumors remain persistently vulnerable to the p53 tumor-suppressor function. Our present study provides compelling evidence that pharmacological activation of the p53 by blocking the MDM2-p53 interaction is a promising cancer therapeutic strategy and MI-219 warrants clinical evaluation as a new cancer therapy," the authors write.

Several study co-authors are employees of Ascenta Therapeutics, Inc., which has licensed technologies related to MI-219 and another MDM2 inhibitor, in which the University of Michigan and another co-author own equity.

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