A DETERGENT in household cleaners may be a powerful weapon against
multidrug-resistant tumours. Canadian researchers say it greatly enhances the
effect of cancer-killing drugs by clogging a protein that cancer cells use to
pump out the drugs.
For over 20 years, researchers have known that if cancer cells produce the
P-glycoprotein pump, they become resistant to a wide range of drugs. But the
same protein is also produced in some healthy tissues, such as the
gastrointestinal tract and the kidney. 鈥淲e understand its role in cancer,鈥� says
Jeffrey Charuk, a biochemist at the University of Toronto. 鈥淏ut we wanted to
know what it was doing normally.鈥�
To find out, Charuk focused on the kidney, since whatever the renal
P-glycoprotein binds to would be pumped into the urine. The problem was that the
pump binds to many commonly used drugs, so the researchers needed a source of
urine guaranteed to be drug-free. Charuk volunteered and collected samples of
his urine for analysis for three years.
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The researchers then treated multidrug-resistant cancer cells with the urine.
They reasoned that any substance that binds to P-glycoprotein should enhance the
ability of anticancer drugs to destroy tumour cells, since the protein would
pump out this substance rather than the drugs. Sure enough, they were able to
purify a chemical that enhanced the killing ability of chemotherapy drugs a
hundred-fold. Even by itself, this substance had some cancer-killing
ability.
The surprise was the substance鈥檚 identity: nonylphenol ethoxylate (NPE), a
synthetic detergent used in dishwasher powder, window cleaners and hard surface
cleansers (American Journal of Physiology: Renal Physiology, vol 274, p
F1127). 鈥淲e were really amazed,鈥� says Charuk.
鈥淭his is important work,鈥� says biochemist Richard B茅liveau of the
University of Quebec in Montreal. 鈥淚t shows the biological role of
P-glycoprotein goes well beyond cancer.鈥� The work suggests, he adds, that
P-glycoprotein evolved to eliminate natural toxins in plants, such as taxol. The
irony is that some of these toxins are now being used as anticancer agents.
鈥淐ancers take advantage of the fact this protein evolved to eliminate any
compound that doesn鈥檛 serve a metabolic use.鈥�
Charuk believes detergents like NPE are attractive candidates for new
anticancer agents because they are inexpensive and abundant鈥攎ore than 600
000 tonnes are produced each year. They are also less toxic than most anticancer
drugs and are easily flushed out of the body. Charuk鈥檚 group is now eager to
test the effect of NPE on tumours in laboratory animals.
There is a downside to NPE, however鈥攊t weakly mimics the hormone
oestrogen. Such chemicals have been blamed for falling sperm counts, and NPE is
banned in many European countries. Charuk believes that he will be able to find
less controversial detergents that can still help kill drug-resistant tumours.
鈥淭here are thousands of similar compounds already commercially available,鈥� he
says.