Natural Compound Reduces Levels of Hormone Action Involved in Prostate Cancer

March 27, 2001. Quercetin, a natural substance found in apples and other fruits and vegetables, significantly reduced the expression of androgen receptor (AR) in the androgen-responsive LNCaP prostate cancer cell line, investigators reported at a cancer research conference in New Orleans.

An androgen receptor is the "lock" that fits the chemical "key" of male hormones that stimulate development and progression of prostate cancer. The LNCaP cell line (pronounced with the letters sounded out - El-En-cap) is used to test drugs and other substances to see if they will work on prostate cancer that is still hormone-sensitive. At this stage the disease responds to drugs like Lupron, Zoladex and Casodex.

"We were attracted to quercetin because it is an abundant natural substance with documented safety," said Nianzeng Xing, M.D., Ph.D., a research fellow in the Urology Department at Mayo Clinic, Rochester, Minnesota.

Quercetin can be found in apples (including the peel), onions, green and black tea, leafy vegetables, beans, and red wine. "According to our preliminary data," Xing said, "quercetin should be a good candidate for prostate cancer treatment because it is a natural compound with relatively low toxicity, and it inhibits the expression and function of the androgen receptor," Nianzeng Xing said.

All untreated prostate cancer starts out sensitive to testosterone and other male hormones, known as androgens, which act through the androgen receptor (eventually the cancer becomes hormone independent, and requires different types of therapy). To deal with hormone-sensitive cancer that has spread beyond the prostate, researchers have long been interested in approaches that disarm androgens as carcinogenic factors by shutting down or reducing the number of receptors.

This is the first research to demonstrate that quercetin has significant activity against AR and results in dose-dependent responses. For doses over 10 µM, quercetin showed significant inhibition of androgen receptor mediated function. A dose of 50 µM induced a dramatic reduction in the levels of two androgen-regulated tumor markers: prostate-specific antigen (PSA; 6.5 times) and hK2 (11 times). The same dose also impeded expression of AR protein by up to 60%.

The Mayo investigators plan to follow this in vitro research with a study of quercetin in a mouse model designed to develop prostate cancer.

Quercetin Inhibits the Expression and Function of the Androgen Receptor in LNCaP Prostate Cancer Cells, Nianzeng Xing, Yi Chen, Susan Mitchell, Charles YF Young, was presented at a Poster Session of the American Association for Cancer Research on March 26 in New Orleans.