FL MORRIS / FMORRIS@STARBULLETIN.COM Dr. Andre Bachmann, assistant professor at the Cancer Research Center of Hawaii, looks at a gel that shows separated proteins of a cancer cell.

UH scientists find molecule that could fight cancer

Work leads to drug that could inhibit growth of tumors

Hawaii researcher Andre Bachmann said he and his colleagues "hit the jackpot" while investigating a molecule called Syringolin A that has anti-cancer properties.

The Cancer Research Center of Hawaii professor, graduate student Crystal Archer and an international team of scientists are experimenting with a drug that uses Syringolin A to interfere with an important part of a cancer cell called proteasome.

"Cancer cells rely on proteasome to do the bad thing they do, to proliferate and grow so rapidly," Bachmann said.

The findings were published in the April 10 issue of the British science journal Nature.

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A new class of molecules that could curb the growth of cancer cells has been discovered by a Hawaii researcher and an international team of scientists.

The molecule is called Syringolin A and it's produced by a bacterium that infects plants, said Dr. Andre Bachmann, assistant professor at the Cancer Research Center of Hawaii.

The researchers found it inhibits the proteasome, "a large cellular machine" that works on cells like a garbage disposal, destroying proteins necessary for cell growth and death in animals, plants and microorganisms.

Proteasomes are found in normal cells, but they are much more important for cancer cells to survive and proliferate, Bachmann said in an interview.

"Certain components make cancer cells go crazy," he said. "If the proteasome is knocked out, they can't grow any more."

Bachmann's research has led to a new type of cancer drug that shuts down the proteasome with fewer side effects than other types of drugs being used, he said.

It's not clear yet when or if the drug will be approved for human use. Bachmann said animal studies must be conducted to evaluate the effectiveness of Syringolin A before doing human clinical studies.

There is a proteasome inhibitor, Velcade, already in use to treat multiple myeloma, Bachmann said.

But Syringolin A has some properties that are better, he said. "The exciting part about this novel molecule is that it not only mimics the way other proteasome inhibitors kill cancer cells, it does so by an entirely new mechanism."

Bachmann experimented with Syringolin A in the laboratory on human cells in ovarian cancer and neuroblastoma, a major form of childhood cancer.

The molecule rapidly entered the cancer cells, blocked the proteasome machine, stopped uncontrolled growth of the cancer cells and killed them, he said.

The team's work was published in the April 10 issue of the scientific journal Nature and discussed in a Nature podcast with Dr. Robert Dudler of the University of Zurich.

"He's on the plant side and discovered the molecule," Bachmann said. "I made the bridge to cancer research."

Bachmann grew up in Switzerland and earned his doctorate degree at the University of Zurich, but did part of his research at the University of Hawaii.

He said Dudler showed him his research on Syringolin A when he went back to Switzerland for a visit about three years ago. Dudler and his colleagues had isolated the molecule while looking for the cause of brown spot disease in green beans. They were surprised to find it prevented the proteasome from breaking down proteins.

Bachmann said Dudler told him the drug might work for cancer. "He sent me a vial and after we got a permit, we started testing."

Assisted by graduate student Crystal Archer in the John A. Burns School of Medicine, Bachmann investigated the molecule as part of the Cancer Research Center's Natural Products and Cancer Biology Program.

The program explores compounds found in nature that chemists can synthesize or engineer for use as anti-cancer drugs, Bachmann said.

"We hit the jackpot in this case. We're so lucky to find the molecule that hits the hot target. A lot of people are interested in killing the activity of the proteasome."

He said Syringolin A binds directly to proteasome. "It also binds to normal cells, but they don't care as much. Cancer cells rely on proteasome to do the bad thing they do, to proliferate and grow so rapidly."

All the cancer-related work was done in Hawaii with contributions from researchers in the United States, Switzerland and Germany, Bachmann said. Among them was Dr. Robert Huber of Max-Planck-Institut fr Biochemie, Germany, a Nobel Prize Laureate in Chemistry.

UH has filed a patent application naming Bachmann, Dudler and Dr. Michael Groll of the Technische Universitat Munchen in Germany as inventors.

Bachmann, first corresponding author of the paper, presented the findings at the recent annual meeting of the American Association for Cancer Research in San Diego.

"I had response in my career like I never had before," said the 40-year-old researcher, who joined the Cancer Research Center in May 2001 and is an adjunct assistant professor in the medical school's Department of Cellular Molecular Biology.

"I had parents coming to me with tears in their eyes looking for ways to cure their kids," Bachmann said. "That's the frustrating part."