Unusual Combination Therapy Shows Promise for Preventing Prostate Cancer

 Combining a compound from broccoli with an antimalarial drug prevents prostate1b drs w and s cancer in mice, University of Pittsburgh Cancer Institute (UPCI) researchers—including McGowan Institute for Regenerative Medicine affiliated faculty members Simon Watkins, PhD, and Donna Stolz, PhD—discovered.

The National Cancer Institute-funded research was published in the journal Cancer Research. It is the first such study to show the effectiveness of the combined treatment and provides compelling evidence for human clinical trials.

“Men with prostate cancer suffer significant impairments in quality of life, not only from the disease itself, but also from the treatments,” said senior author Shivendra Singh, Ph.D., professor in Pitt’s Department of Pharmacology & Chemical Biology. “Because the predominant risk factors for prostate cancer, such as age, race, and genetics, cannot be avoided, there is a great need for preventative treatments for those most at risk.”

Cruciferous vegetables, such as broccoli, watercress, and cabbage, are associated with a lower risk of prostate cancer. The phytochemical sulforaphane in cruciferous vegetables is believed to be responsible.

When scientists tested sulforaphane in the lab, they found it works to prevent early-stage prostate cancer, but not late-stage. Dr. Singh and his colleagues hypothesized that this was due to a cellular mechanism called autophagy, which limits the ability of drugs to destroy cancer.

The antimalarial drug chloroquine inhibits autophagy. When chloroquine and sulforaphane were given to mice predisposed to prostate cancer, only 12 percent of the mice developed late-stage prostate cancer, compared to half in the control group.

“These results are very promising, but I do not recommend that men take chloroquine while eating broccoli in an attempt to prevent prostate cancer,” said Dr. Singh. “Certainly eating broccoli and other cruciferous vegetables is good for you, but chloroquine can have side effects, and it has not been tested in humans for the purpose of preventing prostate cancer.”

Dr. Watkins is founder and director of the Center for Biologic Imaging at the University of Pittsburgh and a member of the Pittsburgh Cancer Institute. He is also the director of the Graduate Program and a professor (with tenure) within the Department of Cell Biology and Physiology. In addition to his responsibilities to the university, Dr. Watkins serves as a member on the research advisory board of Children’s Hospital of Pittsburgh of UPMC.

Dr. Stolz is associate director of the Center for Biologic Imaging and associate professor in the Department of Cell Biology and Physiology at the University of Pittsburgh.

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UPMC/University of Pittsburgh Schools of the Health Sciences Media Relations News Release

Abstract (Chemoprevention of prostate cancer by D,L-sulforaphane is augmented by pharmacological inhibition of autophagy.  Avani R Vyas, Eun-Ryeong Hahm, Julie A Arlotti, Simon Watkins, Donna Beer-Stolz, Dhimant Desai, Shantu Amin, and Shivendra V. Singh.  Cancer Research; published online August 6, 2013.)