Antidepressant May Also Fight Prostate Cancer

Researchers Studying a Behavior-Altering Enzyme Commonly Used in Depression Medications Uncover a Link to Cancer’s Growth and Metastasis in Mice

Contact: Kukla Vera at 323.442.3497 or kvera@pharmacy.usc.edu

An international team of scientists exploring an enzyme known for affecting brain functions and behavior discovered that it also promotes prostate cancer growth in mice.

A new study has found that suppressing the enzyme — monoamine oxidase A, or “MAO-A” — reduced or even eliminated prostate tumor growth and metastasis in mice, opening the door for physicians to possibly use the antidepressant drugs that had targeted MAO-A as a cancer-suppressant as well.

“This is the first paper showing that MAO-A plays an important role in prostate cancer progression and metastasis. MAO-A inhibitors may provide an unmet need in cancer treatment,” said Jean C.  Shih, University Professor at the USC School of Pharmacy, two-time NIH Merit Awardee, and co-corresponding author of a paper on the research that will be published on May 27 in the Journal of Clinical Investigation.

Shih, who has studied MAO-A for 30 years, collaborated with fellow co-corresponding author Leland Chung, a prostate cancer expert from Cedars-Sinai Medical Center. Their team included researchers from the Keck School of Medicine of USC and the Fourth Military Medical University in China. The first author, Boyang Wu was Shih’s doctoral student at USC.

“When this enzyme is not suppressed, it produces a tumor-rich environment that fuels the growth and metastasis of prostate cancer cells,” said Leland Chung, PhD, corresponding author of the paper and director of the Uro-Oncology Research Program at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute. “Suppressing this enzyme and combining it with current therapies may provide a better way to manage and cure men with metastatic prostate cancer.”

MAO-A  regulates the amount of neurotransmitters in the central nervous system by deactivating some — breaking them down. Like all enzymes in the brain, MAO-A is needed in optimum quantities to keep a person healthy. Too much MAO-A has been linked with depression, while too little with autistic behaviors, aggression and anxiety.

Recently, scientists noticed that MAO-A levels were especially high in individuals suffering from prostate cancer — but were unable to determine why.

Shih, Chung, and their team found that MAO-A produces an oxygen-rich, free-radical environment for cancer cells to thrive in — promoting stronger growth and invasiveness. They were able to control this effect in mice, strongly suggesting that the drugs already in existence to inhibit MAO-A for mental depression can do double-duty to suppress prostate cancer.

“We’re happy to be able to translate our discoveries in basic research to clinical application,” said Shih, who is also the director of the USC-Taiwan Center for Translational Research.

Next steps include a Phase II clinical trial of the MAO-A inhibitor in prostate cancer, in collaboration with Mitchell Gross of the Keck School of Medicine of USC and colleagues in USC Norris Cancer Center.

This work was funded by the National Institutes of Health, Grant 5P01CA098912; the Department of Defense PCRP Grant W81XWH-12-1-0282; the USC-Taiwan Center for Translational Research; and the Daniel Tsai Family Fund.