Scientists increasingly are exploring the merits of traditional natural remedies in a quest to find new anticancer compounds, and the efforts seem to be paying off.

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

City of Hope researchers led by Lucy Liu, Ph.D., a recent graduate of City of Hope’s Irell & Manella Graduate School of Biological Sciences, and Richard Jove, Ph.D., Morgan and Helen Chu Director’s Chair of Beckman Research Institute, recently reported that a compound derived from a traditional Chinese cancer treatment might be effective against melanoma, the deadliest form of skin cancer.

The study, published in the June 1 issue of Cancer Research, found that a compound called 6BIO — short for 6-bromoindirubin-3’-oxime — blocks key cancer-promoting proteins in melanoma cells and forces the cells to undergo apoptosis, a type of cell suicide.

6BIO is a chemical derivative of indirubin, the active ingredient in Dang Gui Long Hui Wan, a mixture of 11 herbs and flowers used in traditional Chinese medicine to treat chronic myelocytic leukemia, or CML. Indirubin comes from the indigo plant, an ingredient of the remedy.

Indirubin derivatives that are chemically similar to 6BIO — called bromoindirubins — help form the reddish-blue pigment of some Mediterranean sea shells. Ancient Phoenicians used the pigments more than 2,500 years ago to make Tyrian purple dye for the royal robes of kings and queens.

Scientists in recent years have shown indirubin’s activity not only against CML, but also against other types of cancers such as brain, lung and prostate.

Sangkil Nam, Ph.D., associate research professor in the Department of Molecular Medicine, and Jove earlier discovered one of the ways indirubin and some of its derivatives hamper cancer. The compounds interfere with a protein called STAT3, which promotes cancer growth and development and can protect tumor cells from the immune system.

The current study 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 hampers its cancer-promoting activity.

In addition, 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 mice with human melanoma.

The findings suggest 6BIO may be an effective anticancer agent targeting the JAK/STAT3 system, and the researchers are continuing their studies with the aim of one day testing the compound or related molecules in patients.

Other City of Hope authors on the study include Yan Tian, Ph.D., Fan Yang, Ph.D., Jun Wu, Ph.D., Yan Wang, and Anna Scuto, Ph.D.

The study was supported in part by the National Institutes of Health.