Broccoli Sprouts May Protect Against Bladder Cancer

By Crystal Phend
BUFFALO, N.Y., Feb. 28 -- Even before broccoli matures, the much-maligned vegetable shows promise in prevention of bladder cancer. Rats given high doses of freeze-dried broccoli sprout extract were less than half as likely to develop bladder cancer when exposed to a potent carcinogen as rats not fed the extract, reported Yuesheng Zhang, M.D., Ph.D., of the Roswell Park Cancer Institute here, and colleagues in the March 1 issue of the journal Cancer Research. Broccoli sprouts are a particularly good source of a class of phytochemicals called isothiocyanates, which have been linked to reduced risk of bladder cancer in observational studies.
The sprouts contain about 30 times more isothiocyanates than mature broccoli. The broccoli sprout extract fed to the rats contained about 600 times more.
The daily intake of total isothiocyanate in humans through consumption of cruciferous vegetables is estimated to be 0.14 to 1.43 µmol/kg. Although it's probably not possible to eat enough broccoli sprouts to replicate the doses used in the study (40 to 160 µmol/kg), Dr. Zhang acknowledged, he said it likely wouldn't be necessary.
"The carcinogen exposure we as humans have is going to be much lower than those animals had," he said. "I think if we just simply extrapolate these data to humans, the dose of broccoli sprout extract required to have a similar impact on carcinogenesis is going to be much, much lower."
Dr. Zhang's group previously showed that broccoli sprout extract induced production of enzymes in the bladder that protect against carcinogens and oxidants.
To see whether this would result in lower rates of bladder cancer, the researchers randomly assigned 24 rats to each of five groups.
The control group got regular chow and water. Another group got regular chow but received N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their water as a bladder-specific carcinogen representative of nitrosamines, an important class of human carcinogens.
Another two groups got the carcinogen in their water starting two weeks after initiation of the broccoli sprout extract in their diet at a dose of either 40 or 160 µmol isothiocyanate per kg body weight per day.
The final group received broccoli sprout extract without the carcinogen.
After 12 weeks of treatment, all rats were switched to regular diets and water and were sacrificed 24 weeks later.
None of the rats in the control group or the group that received only the extract developed bladder cancer.
All the rats in the group that received only the carcinogen developed dysplasia (4.2%) or carcinoma (95.8%) of the bladder with an average of 1.96 tumors each.
Broccoli sprouts reduced the likelihood of bladder cancer in a dose-dependent manner.
In the lower dose group, 73.9% of the rats developed cancer (a 22.9% reduction) with an average of 1.39 tumors each a 29.1%).
In the higher dose group, only 37.5% developed cancer (60.9% inhibition) with an average of 0.46 tumors per animal (76.5% inhibition).
Tumor size and progression were similarly lower in extract-treated rats.
Another group of rats sacrificed at various times after being given the broccoli sprout extract showed that isothiocyanate equivalents were rapidly absorbed with a peak at one hour after dosing and excreted in the urine over the next 12 hours.
The researchers said the most remarkable finding was that urinary concentrations were two to three orders of magnitude higher in the urine than in the plasma.
Likewise, levels in the bladder were 2.7 to 3.6 times higher in the bladder than in the liver in the first 12 hours after the extract was given and 19.7 times higher at 24 hours.
Isothiocyanate levels in the bladder epithelium, which is directly exposed to urine, were likely substantially higher than those measured in the bladder tissue overall, Dr. Zhang and colleagues noted, suggesting the isothiocyanate selectively reached the target tissue.
"Given that nearly all bladder cancers occur in the epithelium," the researchers concluded, "isothiocyanate-enriched broccoli sprout extract and other cruciferous vegetables rich in isothiocyanates may be particularly useful for prevention of bladder cancer."
The study was supported by Vital Vegetables Research Program of Australia and New Zealand, which is funded by Horticulture Australia and the New Zealand Foundation for Research Science and Technology; by grants from the National Cancer Institute; and the Roswell Park Alliance Foundation.
One of the authors was a founder of Brassica Protection Products, a company that sells broccoli sprouts, and reported being an unpaid consultant for and owning stock in the company. Neither the broccoli sprout extract used in the present study nor the study itself involved the company.
Primary source: Cancer ResearchSource reference:Munday R, et al "Inhibition of Urinary Bladder Carcinogenesis by Broccoli Sprouts" Cancer Res 2008; 68: 1593-1600.

NSAIDs may protect against bladder cancer

Fri Aug 24, 2:38 PM ET
Regular use of non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, may decrease the risk of bladder cancer, particularly more advanced, high-grade tumors containing alterations in the tumor suppressor protein TP53, results of a study suggest.
The findings also provide further evidence of an increased risk of bladder cancer among users of phenacetin-containing analgesics, particularly long-term users. Phenacetin was withdrawn from the U.S. market in the 1980s after it was implicated in kidney damage and cancer.
For their study, Dr. Margaret R. Karagas of Dartmouth Medical School, Hanover, New Hampshire, and colleagues assessed lifetime use of analgesics and NSAIDs with the bladder cancer incidence in a population-based case-control study. Other common NSAIDs include naproxen (Aleve) and ibuprofen (Motrin).
There were 376 cases of bladder cancer and 463 healthy subjects (controls) from New Hampshire. Overall, 42 percent of the cancer patients and 45 percent of the controls reported regular use of a pain reliever.
Patients with bladder cancer reported regular phenacetin use more than twice as often than the controls did, the researchers report in the current online issue of the peer-reviewed journal BMC Urology. Regular phenacetin users of more than 8 years had a three-fold increased risk of bladder cancer.
In contrast, there was no correlation, overall, between the use of acetaminophen (also known as paracetamol) and risk of bladder cancer.
However, regular use of any NSAID was associated with a statistically significant reduced risk of bladder cancer, an association that was largely due to regular aspirin use. Regular NSAID use seemed to protect against invasive, high-grade and TP53-positive tumors, in particular.
Karagas and colleagues suggest that, "in light of the chemopreventive effects of NSAIDs including aspirin for other neoplasms, the possibility that they may reduce bladder cancer incidence warrants further consideration. Studies assessing the effect on bladder cancer prognosis are lacking but would be of great interest."
SOURCE: BMC Urology, August 10, 2007.

Scientists find one reason why bladder cancer hits more men

Scientists have discovered one of the reasons why bladder cancer is so much more prevalent in men than women: A molecular receptor or protein that is much more active in men than women plays a role in the development of the disease. The finding could open the door to new types of treatment with the disease.
In an article in the April 4 issue of the Journal of the National Cancer Institute, Chawnshang Chang, Ph.D., of the University of Rochester Medical Center and colleagues show that the androgen receptor, which is central to the action of testosterone and other hormones that are much more plentiful in men than women, appears to play a key role in the disease.
In experiments reported in the journal, mice without the receptor had dramatically lower rates of bladder cancer compared to normal mice with the receptor, and human cancer cells with the receptor were much more aggressive than those without it. Mice develop bladder cancer for many of the same reasons people do, and the molecular signals that control cancer development in mice mirror those in humans.
The disease hits about three times as many men as women, including estimates of 50,000 men and 17,000 women in the United States in 2007, according to the American Cancer Society. Some scientists have suspected that male hormones working in concert with the androgen receptor might play a role, but hard evidence has been minimal until now, said Edward Messing, M.D., a bladder cancer expert and chair of Urology. Instead, scientists have suspected that factors like greater exposure of men to cigarettes and industrial chemicals has been responsible.