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July 21, 2008
Magnolia compound strikes cancer target

By Quinn Eastman

A natural compound from magnolia cones blocks a pathway for cancer growth that was previously considered “undruggable,” Emory researchers have found.

The finding is just one example of dermatologist Jack Arbiser’s skill in finding anticancer compounds in the natural world. He has also been probing the properties of curcumin (the bright yellow pigment found in turmeric), gentian violet and mate tea extracts.

His laboratory has been studying the compound honokiol since discovering its ability to inhibit tumor growth in mice and stop tumors from attracting new blood vessels several years ago.

Honokiol comes from magnolia cones and is found in Japanese and Chinese herbal medicines. Reports of its antitumor activity earned international attention in 2003, including television spots showing Arbiser’s co-workers grinding up magnolia cones by mortar and pestle with a satisfying “thwack.”

Now he and his co-workers are closing in on where within the cell honokiol acts as a disruptive monkey wrench. Arbiser’s team’s results describing honokiol’s target were published in the July issue of Clinical Cancer Research. The research was a collaboration with David Foster’s laboratory at Hunter College in New York City.

“Knowing more about how honokiol works will tell us what kinds of cancer to go after,” Arbiser says. “We found that it is particularly potent against tumors with activated Ras.”

Ras refers to a family of genes whose mutation stimulates the growth of several types of cancers. Members of the Ras family are mutated in around a third of human cancers. However, “many of the targets in cancer that are most attractive from a biological perspective are considered intractable from a chemical standpoint,” according to a 2007 commentary by Harvard chemist Gregory Verdine in Clinical Cancer Research.
Honokiol’s properties could make it useful in combination with other kinds of antitumor drugs, because blocking Ras activation could prevent tumors from escaping their effects.

In addition, one of the effects of Ras is to drive pumps that remove chemotherapy drugs from cancer cells.
“Honokiol could be effective as a way to make tumors more sensitive to traditional chemotherapy,” Arbiser says.
In breast cancer cell lines with activations in Ras family genes, honokiol appears to prevent Ras from turning on an enzyme called phospholipase D, Arbiser and his colleagues found. It also has similar effects in lung and bladder cancer cells in the laboratory. Phospholipase D provides what have come to be known as “survival signals” in cancer cells, allowing them to stay alive when ordinary cells would die.

Emory is in the process of licensing honokiol and related compounds so that they can be tested in people in cooperation with industry partners.