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Recently, BMC Cancer reported promising findings from the Nemours Center for Childhood Cancer Research, in Wilmington, about the potential for components of a common spice to be effective in treating brain tumors in children and in identifying which children may derive the most benefit.
Brain tumors are the second most frequent malignant tumors in children and are associated with poor prognoses and outcomes when compared with other common pediatric cancers. Among pediatric brain tumors, medulloblastoma is the most common malignant form. Despite advances in treatment, favorable outcomes lag behind many other childhood cancers and therapy often results in severe long-term side effects. Thus, it is imperative to identify safer, more effective treatments for medulloblastoma.
Curcumin, a major component of the spice turmeric, has been gaining ground in the scientific community as a promising cancer treatment agent. Curcumin is derived from the plant Curcuma longa and has been used for centuries in India and other parts of Southeast Asia as a cooking spice and a medicine.
Recently, curcumin has gained wider attention and is considered a valuable candidate for clinical development due to its effectiveness in treating cancers and its lack of adverse reactions in adults or children. Curcumin is thought to have antioxidant properties, which means it may decrease the inflammation that appears to play a role in cancer.
While it is known that curcumin preferentially targets cancer cells, at this point there are no biomarkers to predict which cancer patients would benefit from curcumin therapy.
In studies conducted and published in 2011, Sigrid Langhans, PhD, and her team at
the Nemours Center for Childhood Cancer Research, evaluated curcumin as a potential therapeutic for medulloblastoma. They showed that curcumin can kill human medulloblastoma cells cultured in the laboratory. But more importantly, they also
found that curcumin reduces tumor growth and increases survival in models of medulloblastoma.
This finding is very important because it shows that curcumin can be effective in crossing the blood-brain barrier. In many instances, the failure of treatment for brain tumors is not due to lack of potency of the drugs, but instead due to the failure of these drugs to reach the brain because of their inability to cross the blood-brain barrier. The blood-brain barrier protects the brain from potentially toxic substances in the blood, but it also impedes efficient drug delivery.
Nemours researchers’ finding that curcumin can be effective in the brains of mice to reduce medulloblastoma growth suggests that curcumin has the potential to be developed as a therapeutic for medulloblastoma without the severe side effects of current treatment regimens.
In a follow-up to last year’s study, Dr. Langhans and team were able to identify a protein as a candidate biomarker to predict which patients might respond favorably to curcumin therapy. They found that curcumin binds to and crosslinks a specific protein (Cdc27/APC3), halting cell growth at a “checkpoint” for extended times thus forcing
the cells to undergo programmed cell death. Importantly, checkpoint proteins are
tightly regulated during normal cell growth and are often being modified depending on the cell cycle.
Langhans found that curcumin binds more resolutely to this specific protein when it is phosphorylated, a modification usually found in fast-growing cells such as cancer cells. They further found that these cells are much more susceptible to curcumin-induced cell death than cells that have only the unphosphorylated protein. The results not only provide a possible explanation for why curcumin targets tumors with minimal side effects on normal cells, but also suggest that the phosphorylation status of the protein could be developed as a biomarker to predict which patients might respond favorably to curcumin-based cancer therapy.
The work of Dr. Langhans and the Nemours Center for Childhood Cancer Research holds promise for the treatment of brain tumors in both children and adults. Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis: BMC Cancer.
About Nemours Center for Childhood Cancer Research
The Nemours Center for Childhood Cancer Research (NCCCR) is a research entity of Nemours Biomedical Research at the Nemours/Alfred I. duPont Hospital for Children. The goal of the center is to evolve into a leader in research focusing on biomarkers for childhood cancers and cancers that affect families. The NCCCR works with the Christiana Care Helen F. Graham Cancer Center, the University of Delaware Center for Translational Research, and the Delaware Biotechnology Institute.