Drug Used to Treat Cholesterol Prevents Growth of Breast Cancer Cells in Lab

 

 

Behind the Cancer Headlines®

April 8, 2003

 

 

Statin drugs used to lower cholesterol may also help prevent development of breast cancer, say researchers who studied the drugs in laboratory cell cultures.

 

The investigators, from The University of Texas M. D. Anderson Cancer Center, found that a side effect of drugs such as lovastatin and Zocor is to allow body cells to maintain high levels of proteins that stop cancer cells from growing.

 

Their findings were presented at the Annual Meeting of the American Association for Cancer Research.

 

"We have found out how a well-known and widely used class of drugs exhibits anti-cancer activities, and that's an exciting finding," says the lead investigator, Ekem Efuet, a postdoctoral researcher working in the lab of Khandan Keyomarsi, Ph.D., associate professor in experimental radiation oncology.

 

Additionally, the researchers found that the biological mechanism used by statin drugs to prevent cancer growth may also be the same one used by experimental farnesyl transferase inhibitors now being clinically tested as a cancer treatment. "We think these experimental agents are targeting the protein degradative pathway, the same way that the statins do," says Keyomarsi.

 

Most of the dose of statin drugs that patients take is converted from its inactive to active form in the liver and used to prevent the synthesis of cholesterol. But the inactive form of the drug that remains in small quantities in the body proves to be a potent cancer fighter, says Efuet.

 

Several years ago, Keyomarsi’s lab found that applying lovastatin to cultures of breast cancer cells arrested any further growth, and so they worked to determine what the drug does to produce anti-cancer effects.

 

They found that the pure, unconverted form of the drug (the "closed ring, prodrug" form) stopped cells from activating its proteasome "garbage disposal" to degrade extra P21 and P27 cyclin dependent kinase inhibitors in the cells. These proteins, also known as the brakes of the cell cycle, have been shown to inhibit cancer growth, and so a build-up of P21 and P27 in cells may help prevent cancer formation, say researchers.

 

On the other hand, the converted ("open ring") form of statin drugs - the form of the drug that lowers cholesterol - was found to have little such anti-cancer activity, proving that the drug works in two different ways, depending on its structure.

 

The researchers suggest that potent anti-cancer drugs could be developed based on the unconverted form of statins, and they expect to begin testing statin drugs that have already been approved in animal cancer experiments soon.

 

 

SOURCES:

 

Annual Meeting of the American Association for Cancer Research, April 7, 2003, Toronto, Canada

University of Texas M.D. Anderson Cancer Center (http://www.mdanderson.org)