Indirubin: Component of Chinese herbal remedy might block brain tumour's spread

Dr. E. Antonio Chiocca.

The researchers discovered that the compound, indirubin, both blocks the migration of glioblastoma cells, preventing their spread to other areas of the brain, and the migration of endothelial cells, preventing them from forming the new blood vessels that the tumour needs to grow.

Glioblastomas occur in about 18 500 Americans annually and kill nearly 13 000 of them yearly. Glioblastoma multiforme is the most common and lethal form of the malignancy, with an average survival of 15 months after diagnosis.

The research is published online in the journal Cancer Research.

Indirubins offer a novel therapeutic strategy

"We have pretty good methods to stop glioblastoma from growing in the human brain, but these therapies fail because tumour cells migrate from the original site and grow elsewhere in the brain," says co-principal investigator Dr. E. Antonio Chiocca, professor and chair of neurological surgery and co-director of the Dardinger Centre for Neuro-oncology and Neurosciences.

"Our findings suggest that indirubins offer a novel therapeutic strategy for these tumours that simultaneously targets tumour invasion and angiogenesis," Chiocca says.

"This study shows for the first time that drugs of the indirubin family may improve survival in glioblasoma, and that these agents inhibit two of the most important hallmarks of this malignancy - tumour-cell invasion and angiogenesis," says co-principal investigator Dr. Sean Lawler, senior scientist and group leader of the Translational Neurooncology Group at the Leeds Institute of Molecular Medicine.

Derived from the indigo plant

Indirubin is derived from the indigo plant. It is the active ingredient in the Chinese herbal remedy called Dang Gui Long Hui Wan, which is used to treat chronic myeloid leukaemia.

Chiocca, Lawler and their collaborators used multiple glioblastoma cell lines and two animal models to examine three derivatives of indirubin. Key findings include the following:

• When human glioblastoma cells were transplanted into one brain hemisphere of mice, the indirubin-treated animals showed significantly longer survival, and there was no migration of tumour cells to the opposite hemisphere of the brain.

• In a separate experiment, indirubin reduced the migration of tumour cells by 40% in treated animals versus controls.
  
• Treated tumours showed a lower density of blood vessels, and new blood-vessel growth was reduced up to three-fold in intracranial tumours, depending on the tumour-cell line.

• A laboratory assay showed that indirubins reduced endothelial-cell migration by 52 to 41% compared with untreated controls.

"Overall, our findings suggest that indirubins reduce tumour invasion and tumour vasculature because of their antimigratory effects on both tumour and endothelial cells," Chiocca says.

E. Antonio Chiocca, MD, PhD, is the Dardinger Family Professor of Oncologic Neurosurgery.

Funding from the Esther L. Dardinger Endowment for Neuro-oncology and Neurosciences, the National Cancer Institute, the Jeffrey Thomas Hayden Foundation and the American Brain Tumour Association supported this research.

Other Ohio State researchers involved in this study were Shanté P. Williams, Michal O. Nowicki, Fang Liu, Rachael Press, Jakub Godlewski, Mahmoud Abdel-Rasoul, Balveen Kaur and Soledad A. Fernandez.

The Ohio State University Comprehensive Cancer Centre - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute ( cancer.osu.edu) is one of only 40 Comprehensive Cancer Centres in the United States designated by the National Cancer Institute and was recently awarded the highest ranking possible - exceptional - by NCI. Ranked by US News & World Report among the top cancer hospitals in the nation, The James is the 205-bed adult patient-care component of the cancer program at The Ohio State University. The OSUCCC - James is one of only seven centres in the country funded by the NCI to conduct both phase I and phase II clinical trials.

Source: Ohio State University