Discovery of new compound known as SP-4-84 could lead to improved chemotherapy treatments

Dec 20 2004

The discovery of a new compound by Michigan State University researchers could lead to improved chemotherapy treatments for different types of cancers – potentially with fewer side effects.

The discovery of the compound – known as SP-4-84 – was made by an MSU team led by Jetze Tepe, an assistant professor of chemistry, and is detailed in the December issue of the journal Chemistry & Biology.

The researchers believe that the compound, when used in conjunction with chemotherapy drugs such as cisplatin and camptothecin, can make the anti-cancer drugs much more effective.

“This may potentially mean that one could use less than one-tenth of the current drug dosage and still get the same therapeutic results – but fewer side effects – or use the same drug dosage which is now much more effective in its treatment,” Tepe said.

Even though this new compound is in the earliest stage of development, this is potentially good news for the millions of Americans diagnosed with cancer every year. The national Centers for Disease Control and Prevention says more than a half-million Americans die of cancer every year, second only to heart disease.

Here is how the newly discovered compound works: Most anti-cancer drugs work by causing cell damage, such as DNA damage, which ultimately kills the cancer cells. However, cancer cells are also prone to repair themselves and survive the damage done by drugs, which renders the drugs less effective.

Tepe and his colleagues found that when SP-4-84 was added to certain anti-cancer drugs, it inhibited the cancer cell’s ability to survive chemotherapeutic treatment.

“Essentially,” he said, “it sensitizes only cancer cells to chemotherapeutics by blocking the cancer cell’s ability to survive the damage that was caused by the chemotherapeutic drugs.”

Another problem with chemotherapy drugs is that they generally don’t discriminate between cancer cells and healthy cells. The drugs basically damage all cells that are continuing to replicate.

“So, if we’re able to give the patient a drug that remains as effective despite a smaller dose, this could spare the patient a lot of side effects such as severe nausea, kidney or liver damage, and other side effects typically experienced during chemotherapy,” Tepe said.

“Tests preformed with cancer cells in culture found that over a 48-hour period small amounts of SP-4-84 made camptothecin 75 times more effective that conventional treatment,” he said. “However, when we used the compound on non-cancerous cells, there was absolutely no effect. It appears right now that the compound is only selective for cancer cells.”

Thus far, SP-4-84 appears to be extremely non-toxic, he said.

In their current work, Tepe and his co-workers have teamed up with MSU’s Carcinogenesis Laboratory, where the teams are evaluating the new compound in mice.

“As with all new discoveries, much more work needs to be done to evaluate the potential of this compound for its ability to improve conventional therapeutic treatment,” Tepe said.

Other members of Tepe’s team include graduate students Vasudha Sharma and Satyamaheshwar Peddibhotla, and research associate Theresa Lansdell.