Synthetic Detergent Found To Fight Multi-Drug Resistance

The detergent reduces the amount of chemotherapy drugs required to treat multi-drug resistance by blocking a drug pump in cancer cells. The researchers found the synthetic detergent in human urine while looking at the role of the drug pump in the kidney.

"We're very surprised by these findings," says lead investigator Dr. Jeffrey Charuk of the department of medicine. "While the synthetic chemical is probably too low to interfere with the action of the drug pump it might be a useful adjunct to standard chemotherapy treatments, along with other relatively non-toxic detergents."

"Detergents are composed of compounds that can be chemically synthesized to suit your needs," says Charuk. "With our study completed, the next critical step is for clinicians to evaluate the use of these compounds in treating cancer."

Charuk collected his own urine for three years to determine the role of the drug pump in the kidney. Together with co-investigators Dr. Reinhart Reithmeier of the department of medicine and Dr. Arthur Grey of the department of medical genetics and microbiology he developed a sensitive test to detect the compound by nuclear magnetic resonance and mass spectroscopy. The test revealed the synthetic detergent, nonylphenolethoxylate (NPE), a common component in hard surface and household cleansers, is present in human urine. The detergent can be absorbed into the body through skin when it contacts people's hands or it can be ingested when people eat from dishes that have been washed with the compound.

"The effect of long-term exposure to the detergent needs to be studied," explained Charuk, who also notes further research is needed to show how the biodegradation of detergents like NPE affects the environment. "NPE degradation can result in the production of alkylphenols and these compounds are hormone disrupters that can interfere with the growth and development of animals."

The pump, referred to as P-glycoprotein, was discovered in 1976 by Dr. Victor Ling of the Ontario Cancer Institute. P-glycoprotein is found in high levels in the cell membranes of certain cancer cells that are resistant to a wide variety of anti-cancer drugs. Tumors that contain a high content of P-glycoprotein fail to respond to chemotherapy because the pump rapidly removes these drugs from cells, preventing their killing action. The pump is also found normally in the intestine and liver although its role in these tissues is not known. In the kidney it functions by moving substances from blood in the kidney through the wall of a cell and into urine.

"For decades the kidney has been identified as playing an important role in protecting the body from natural and synthetic chemicals in the environment," says Reithmeier. "Our study illustrates this concept beautifully." Investigators Charuk and Reithmeier received financial support from the Kidney Foundation of Canada and the Medical Research Council of Canada.

CONTACT:
Kerry Delaney
U of T Public Affairs
(416) 978-5948
E-mail: kerry.delaney@utoronto.ca