Kava Root Compound Shows Promise for the Prevention of Bladder Cancer

Division of Cancer Prevention

Exposure to carcinogens from both tobacco and those associated with working in some industries are known risk factors for bladder cancer. Bladder cancer researchers are interested in certain chemicals in foods or dietary supplements that may help protect against tumor formation and those that naturally concentrate in the urine and pass through the bladder.

Xiaolin Zi, Ph.D., associate professor of urology at the University of California, Irvine, is examining a compound found in kava root called flavokawain A as a potential bladder cancer preventative.

“In the western Pacific islands, where people drink kava beverages like we drink wine, incidences of bladder cancer are low despite high smoking rates,” Dr. Zi noted. “I’ve been investigating whether kava extracts, specific chemical components in kava extracts, or combinations of kava chemicals have anti-bladder cancer activity, and if so, how specific kava compounds can be used for preventing bladder cancers in smokers or even for reducing the risk of bladder cancer recurrence.”

In earlier studies,* Dr. Zi and his colleagues performed extensive laboratory analyses of the chemical components of kava root extract, including several belonging to a chemical family called the chalcones. The chalcone flavokawain A had the strongest antiproliferative effect (reducing cell division) and apoptotic effect (causing cell death) in human bladder cancer cell lines derived from several different stages of the disease.

Further studies** showed that the effects of flavokawain A are dependent on a gene called p53, a known tumor-suppressor gene that is mutated in many tumor types. Bladder cancer cells with defective p53 were actually more sensitive to growth inhibition by flavokawain A. The kava compound appears to induce apoptosis by re-activating several genes normally controlled by p53 through a complex cell-signaling pathway, Dr. Zi explained.

Flavokawain A also reduced tumor growth by 64 percent in mice implanted with bladder cancer cells in these studies. With NCI funding,*** Dr. Zi is currently exploring flavokawain A’s anti-cancer effects in several more complex mouse models of bladder cancer, in a series of experiments expected to conclude in 2012.

In one of these models, mice are exposed to the carcinogen 4-hydroxybutyl (butyl) nitrosamine (OH-BBN), which causes tumors that mimic bladder cancer development in smokers. “This model will be used to test the usefulness of flavokawain A for preventing the occurrence of bladder cancer in heavy smokers,” explained Dr. Zi.

Two additional transgenic mouse models of bladder cancer will also be used. “These models recapitulate two different molecular pathways leading to two different types of bladder cancer,” said Dr. Zi. “We’ll use these models to test if flavokawain A can decrease the recurrence of bladder cancer or prevent the progression of bladder cancer into invasive disease, what’s sometimes called secondary prevention.”

Dr. Zi noted, “Available treatments for preventing bladder cancer recurrences are associated with significant toxicities. We hope that flavokawain A or its derivatives will be a non- or less-toxic oral agent for preventing bladder cancer recurrence, and also for bladder cancer prevention in heavy smokers and people working in a number of high-risk industries.”

NCI Program Director for the study Vernon Steele, Ph.D., M.P.H., commented, “Preventing bladder cancer recurrence and bladder cancer prevention are important goals in the field of cancer prevention. This is especially true in heavy smokers and people working in high-risk occupations. Hopefully, flavokawain A or its analogues will be non- or less-toxic oral agents for preventing bladder cancer recurrence and prevention. Positive animal results in a cancer prevention model will help support further development of these agents.”