summary: Indirubin, a natural product found in the indigo plant and used in Chinese medicine, improves survival in mouse models of glioblastoma brain cancer.
source: Brown University
A new study shows how a drug made from a natural compound used in traditional Chinese medicine works against malignant brain tumors in mice, creating a promising area of research in the treatment of glioblastoma.
In the study published in Medicine Cell ReportsIn this study, the researchers showed how the combination of the compound, called indirubin, improved the survival of mice with malignant brain tumors.
They also tested a new formulation that was easier to administer, taking the potential pharmaceutical approach a step closer to clinical trials with human participants.
“The interesting thing about this drug is that it targets a number of hallmarks of the disease,” said Sean Lawler, lead author and associate professor of pathology and laboratory medicine at Brown University. This is attractive because this type of cancer keeps finding ways to get around the individual mechanisms of attack. So if we use multiple attack mechanisms simultaneously, maybe it will be more successful.”
The research team included scientists from the Brown Legoretta Cancer Center and the College of Engineering. Department of Neurosurgery at Brigham and Women’s Hospital/Harvard Medical School; and Phosphorex, Inc./Cytodigm, Inc.
Glioblastoma is the most common and dangerous type of brain cancer. The standard of care is chemotherapy, radiation, and surgery, which may improve symptoms but do not cure or stop the cancer.
Indirubin is a natural product found in indigo plants and a component of traditional Chinese medicine Dang Gui Long Hui Wan, which has been used in the treatment of chronic myelogenous leukemia, according to the researchers. Indirubin derivatives have shown potential to treat cancer through a range of mechanisms.
Research published 10 years ago by Lawler et al showed that indirubin slows the growth of glioblastoma tumors in mice. However, he said, the researchers were unable to explain why. Moreover, the altered drug was not very easy to handle, making it difficult for scientists to test dose levels or efficiently deliver it to a tumor.
As the scientists continue to search for the compound, they have been contacted by the Massachusetts-based biomedical company Phosphorex, which is developing technology to improve pharmaceutical formulations. Phosphorus patented a formulation of indirubin called 6′-bromoindirubin acetuxime (BiA), which made the compound easier to use as an injectable cancer treatment.
The researchers tested the BiA nanoparticle formulation on glioblastoma tumors in mice, focusing on how the drug affects the immune system.
Not only did BiA slow the growth and proliferation of tumor cells (confirming the findings of previous studies), but it also improved survival through effects on important immunotherapy targets.
“The drug affected the immune system in these mouse experiments in a way that we believe could enhance clinical immunotherapy in humans,” explained Lawler, who uses in vitro therapeutic approaches to treat brain cancer.
The researchers will continue to test the drug to see how it interacts with chemotherapy and radiation, with the goal of developing clinical trials for participants with glioblastoma. While scientists have been studying glioblastoma for decades, Lawler said there haven’t been many significant treatment breakthroughs, until now.
“Over the past 20 years or so, there haven’t been many findings that have really affected survival in a meaningful way, so we’re very eagerly looking for new approaches,” said Lawler. “This research offers a new approach, which is why we’re very excited about it.”
About this brain cancer research news
author: press office
source: Brown University
communication: Press Office – Brown University
picture: The image is in the public domain
Original search: open access.
“PPRX-1701, a nanoparticle formulation of 6′-bromoindirubin acetoxime, improves delivery and shows efficacy in preclinical GBM models” by Mykola Zdioruk et al. Medicine Cell Reports
PPRX-1701, a nanoparticle formulation of 6′-bromoindirubin acetoxime, improves delivery and shows efficacy in preclinical GBM models.
- PPRX-1701 is a deliverable formulation of 6-bromoindirubin-3′-acetuxime (BiA)
- It inhibits IDO1 expression and increases CD8 T cell infiltration in GBM mouse models
- Data support investigation into this approach for potential future translation
Derivatives of the traditional Chinese drug indirubin have shown potential to treat cancer through a range of mechanisms. This study investigates the effect of 6′-bromoindirubin-3′-acetoxime (BiA) on immunosuppressive mechanisms in glioblastoma (GBM) and evaluates the efficacy of a BiA nanoparticle formulation, PPRX-1701, in GBM models of immunocompetent mice.
Transcription studies reveal that BiA downregulates immune-related genes, including indoleamine 2,3-dioxygenase 1 (IDO1), an enzyme important in the tryptophan-kynurenine-aryl hydrocarbon receptor (Trp-Kyn-AhR) immunosuppressive pathway in cancer cells. . BiA blocks interferon-γ (IFNγ)-induced IDO1 protein expression. in the laboratory It enhances T-cell-mediated tumor cell killing in GBM stem cell co-culture models. PPRX-1701 reaches intracranial GBM and significantly improves survival in immunocompetent GBM models He lives.
Our results indicate that BiA improves survival in murine GBM models through effects on important immunotherapy targets in GBM and that it can be efficiently delivered via PPRX-1701, an injectable nanoparticle formulation of BiA.