About 2,500 years ago, the ancient Phoenician people stumbled across a way to pull chemicals from the mucous of local sea snails to create a rich purple dye. This Tyrian purple was rare, expensive and reserved for nobility.

In modern times, scientists have explored these compounds and their relatives for a different kind of noble cause — treating cancer and other diseases.

Lucy Liu is studying the anticancer activity of a compound stemming from a natural remedy. (Photo by Darrin S. Joy)

Researchers now know that the compounds that make Tyrian purple are bromoindirubins, chemical relatives of indirubin, itself a naturally occurring chemical with known healing properties.

For instance, the traditional Chinese medicine Dang Gui Long Hui Wan is used to treat a form of leukemia. Among its mixture of 11 herbs and flowers is indigo — which contains indirubin.

Scientists have shown indirubin’s activity against brain, lung and prostate cancers, as well.

Wanting to know more about how indirubin works, Sangkil Nam, Ph.D., associate research professor in the Department of Molecular Medicine, and Richard Jove, Ph.D., Morgan and Helen Chu Director’s Chair of Beckman Research Institute, studied the chemical and some of its derivatives to find out how they hamper cancer. They found that the compounds interfere with a protein called STAT3, which promotes cancer growth and development and can protect tumor cells from the immune system.

More recently, a team led by Jove and Lucy Liu, Ph.D., a recent graduate of City of Hope’s Irell & Manella Graduate School of Biological Sciences, focused on another compound called 6-bromoindirubin-3’-oxime, or 6BIO. It’s a chemical derivative of those bromoindirubins found in the Phoenicians’ seashells.

The researchers found that 6BIO works by blocking a group of proteins called Janus activated kinases, or JAKs, which activate STAT3. By blocking JAKs, 6-BIO inhibits STAT3 activation and hinders its cancer-promoting activity. It also helps push the cancer cells to undergo apoptosis, a form of programmed cell suicide.

6BIO was the most effective indirubin derivative of all of the compounds the group tested, suppressing tumor cell growth more than three times as effectively as indirubin itself.

“Many times we find the active ingredient in a natural or traditional remedy is effective but can be improved with some modification,” Liu said.

Importantly, 6BIO also suppressed tumor growth and demonstrated low toxicity in laboratory studies.

The findings suggest 6BIO may be an effective anticancer agent targeting the JAK/STAT3 system.

The researchers are continuing their studies with the aim of one day testing the compound or related molecules in clinical trials.