Dual-action compound shows promise in killing prostate cancer cells

Aug 22 2004

Ohio State University researchers are working on developing a multi-purpose cancer drug that might one day scale back the number of medications some cancer patients need to take.

In laboratory tests, a dual-action compound called OSU 111 has shown promise in killing prostate cancer cells.

"It had a direct toxic effect on cancer cells, and also prevented angiogenesis – the formation of new blood vessels from pre-existing ones," said Tom Li, the study's lead investigator and an associate professor of pharmacy at Ohio State.

"It's like using one stone to kill two birds."

Li presented the results on August 22 in Philadelphia at the summer meeting of the American Chemical Society.

OSU 111 is a variation on a theme – Li and his colleagues created OSU 111 using a known anti-cancer compound, SU-5416, as a model. Although SU-5416 showed promise in preclinical studies, it did not have the kind of far-reaching effectiveness that researchers had hoped for.

But SU-5416 does provide a good blueprint by which researchers can create dozens of analogs – compounds structurally similar, but with slightly different chemical compositions.

"We've made close to 50 different analogs by modifying SU-5416," Li said.

Laboratory experiments show that OSU 111 is one of the most promising analogs for killing cancer cells Li's team has found so far. When treated with OSU 111 in laboratory experiments, the majority of prostate cancer tissue cells died within three days, Li said.

"This compound stopped cell division in its tracks," he said.

OSU 111 induces apoptosis – cell suicide – in cancer cells because it keeps key structures called microtubules from working during cell division. Microtubules distribute chromosomes to new cells. OSU 111 also prevents tumor cells from forming new blood vessels.

Scientists are looking for alternatives to established anti-cancer drugs, such as Taxol, which is used to kill cancer cells in ovarian, breast and lung tissue. Drugs like Taxol come from natural sources, and supplies are sometimes extremely limited. Also, synthetic versions of these drugs can be very difficult to make.

Providing a drug with more than one effect could also benefit cancer patients who are inundated with medications.

"Many clinical trials that test new cancer treatments use a combination of drugs – one to prevent the growth of new blood vessels, for example, and another to keep cancer cells from dividing and spreading," Li said. "One drug with dual activity means that the body only has to deal with a single compound, and that could eliminate a lot of complexity in terms of giving medication to patients, the body's ability to absorb a drug and also side effects.

"We want to find a drug with a dual purpose," he continued. "Angiogenesis is very prominent in many cancers, particularly prostate cancer. Pure anti-angiogenic compounds haven't been that successful; somehow cancer cells still find a way to form blood vessels."

Li and his colleagues are continuing to look for even more potent analogs based on the structure of SU-5416.

"We're developing small, easy-to-make compounds that are similar to established drugs, but hopefully much easier to come by," he said.

Li conducted this work with Ohio State colleagues Bulbul Pandit, Zhigen Hu, Zili Xiao and Christine Cheah; and Dan Sackett, of the Laboratory of Integrative and Medical Biophysics at the National Institute of Child Health and Human Development.