A laboratory led by Jack Arbiser MD PhD, at Emory University School of Medicine, USA, has been studying the compound honokiol, found in Japanese and Chinese herbal medicines, since discovering its ability to inhibit tumour growth in mice in 2003.
Arbiser’s team’s results were published in the July issue of Clinical Cancer Research.
“Knowing more about how honokiol works will tell us what kinds of cancer to go after,” says Arbiser, who is an associate professor of dermatology. “We found that it is particularly potent against tumours with activated Ras.”
Ras refers to a family of genes whose mutation stimulates the growth of several types of cancers. Although the Ras family is mutated in around a third of human cancers, medicinal chemists have considered it an intractable target.
Honokiol’s properties could make it useful in combination with other antitumour drugs, because blocking Ras activation would prevent tumors from escaping the effects of these drugs, Arbiser says.
“Honokiol could be effective as a way to make tumours more sensitive to traditional chemotherapy,” he says.
One of the effects of Ras is to drive pumps that remove chemotherapy drugs from cancer cells. 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 University is in the process of licensing honokiol and related compounds so that they can be tested in people in cooperation with industry partners.