“Cigarette smoking is a leading cause of bladder cancer, but in the Pacific
islands, where kava is plentiful, the incidence of cancer is low despite high
smoking rates,” he says. “What I’ve been investigating is how kava compounds can
prevent bladder cancer in smokers.”
Since joining UC Irvine in 2002, Zi has studied bioactive agents that come
from such plants as the tomato and kava for their chemopreventive impact on prostate and bladder cancer.
Currently, he’s focused on the kava-derived flavokawain A. With funding from
the National Cancer Institute, Zi’s team is using mouse models of
bladder cancer to demonstrate its efficacy in protecting against the
carcinogenic influence of tobacco.
They’ve found that flavokawain A encourages apoptosis, or cell death, in
precancerous cells by overcoming the effects of the mutated p53 protein. Known
as “the guardian of the genome,” this protein plays a critical role in keeping
cells from becoming cancerous, but it’s defective in about half of all human
cancers.
(Earlier this year, University of Minnesota researchers published study
results in which flavokawain A treatments blocked the proliferation of breast
cancer cells.)
Zi’s group has set out to show that mice fed high doses of flavokawain A
experience a corresponding slowing of tumor growth. Initial data have been very
promising. All three bladder cancer mouse models have responded to the
treatment.
To date, Zi has seen no evidence of toxicity from the flavokawain A compound.
He notes that this is critical to the compound’s potential as a therapy for
human bladder cancer patients.
“The majority of bladder cancer occurs after age 65. Any agents that can
delay the onset of cancer are highly beneficial,” says Zi, who’s also a member
of UC Irvine Health’s Chao Family Comprehensive Cancer Center. “For older
people, being cancer-free for years longer dramatically improves quality of
life.”
More than 70,000 new cases of bladder cancer are reported annually in the
U.S. The per-patient cost to the nation’s healthcare system of bladder cancer is
among the highest of all cancers ($96,000 to $187,000).
Although there are numerous options for the treatment of bladder cancer and
success rates are high compared with many other solid-tumor malignancies, the
American Cancer Society estimates that nearly 15,000 Americans will die from
bladder cancer this year. Many of the current chemotherapeutic treatment
regimens for bladder cancer also carry significant side effects and
toxicities.
Treatments derived from natural sources, Zi says, may provide a solution. He
hopes to conduct clinical trials on human patients in the near future.
“Although there are not yet a lot of studies showing the cancer-fighting
effectiveness of natural treatments, many cancer patients are using them,” he
adds. “More studies are needed to find out if these natural supplements work and
in what circumstances people should use them. There’s a lot of exciting
potential in this area of research.”