(From the September 2013 Issue of PediatricsOnline)
A new study of two plant-derived compounds suggest they may stunt tumor growth caused by neurofibromatosis type 2 (NF2), a genetic disorder that affects one in every 25,000 people in the U.S. Individuals afflicted by NF2 frequently develop multiple nervous system tumors, including vestibular schwannomas, benign tumors that form along the nerve controlling hearing and balance, and meningiomas, which grow from the lining of the brain. The research, led by Long-Sheng Chang, PhD, in The Research Institute at Nationwide Children’s Hospital, offers hope to people with the disease, which usually strikes during adolescence and can cause bilateral deafness, cataracts, vertigo, facial nerve paralysis and brainstem compression.
Currently, there are no approved drug therapies for NF2. Although surgery and radiation can help, these treatments are associated with significant complications and, in some cases, the location or number of tumors renders them inoperable. Tumors often return and multiply fast. Radiation can increase the risk that these benign growths will develop into cancer. These arguments demonstrate the need for an effective medical treatment for vestibular schwannomas and meningiomas, Dr. Chang says. The anti-tumor properties in many natural compounds have been used in a number of successful therapeutics, including such drugs as taxol, one of the most effective drugs against breast and ovarian cancer.
“Natural compounds have been used widely in cancer chemotherapy and are a particularly attractive solution for therapy in benign disease that is often slow growing,” says Dr. Chang, a principal investigator in the Center for Childhood Cancer and Blood Diseases and senior author of the new study, which was published online in August in the journal Otology & Neurotology.
NF2 is caused by mutations in the neurofibromin 2 gene, which provides instructions for making a protein called merlin, or schwannomin. Primarily found in the Schwann cells that surround and insulate nerve cells in the brain and spinal cord, the exact function of merlin is unknown. Scientists suspect the protein acts as a tumor suppressor and is involved in regulating cell signaling, movement and shape. Genetic mutations lead to dysfunctional versions of the protein, which allow cells to multiply and form tumors.
In collaboration with Ohio State University faculty D. Bradley Welling, MD, PhD, in the Department of Otolarngology/Head & Neck Surgery, and A. Douglas Kinghorn, PhD, in the College of Pharmacy, Dr. Chang’s team screened 20 plant-derived compounds found to be highly toxic to one or more types of cancer. Two compounds in particular caught their attention—cucurbitacin D and goyazensolide. Cucurbitacin D is a steroid secreted by certain members of the Cucurbitaceae plant family, which includes pumpkins and gourds, to ward off herbivores. Goyazensolide is a chemical secreted by plants in the daisy family called Piptocoma rufescens.
When the researchers injected the compounds into cell cultures derived from tumors developed in mice lacking the NF2 gene or from human tumor specimens, the proliferation of both schwannoma and meningioma cells was effectively retarded. They also found a decrease in the levels of several key growth-signaling molecules in treated cells.
Although the work is still preliminary, the findings are promising, says Dr. Chang, who also is a professor of pediatrics at The Ohio State University College of Medicine.
“The next step will be further in vivo testing of these two natural compounds using relevant animal models,” Dr. Chang says. “This would allow us to better study their potential as chemotherapeutic agents for NF2-associated tumors.”
Spear SA, Burns SS, Oblinger JL, Ren Y, Pan L, Kinghorn AD, Welling DB, Chang LS. Natural Compounds as Potential Treatments of NF2-Deficient Schwannoma and Meningioma: Cucurbitacin D and Goyazensolide. Otology & Neurotology. 2013 Aug 7. [Epub ahead of print]
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