Drug Forms of Chinese Herbal Compounds Found to Improve Survival in Brain Tumor Models

summary: Indirubin, a natural product found in the indigo plant and used in herbal medicine, improved survival in a mouse model of glioblastoma brain tumor.

sauce: 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, a promising study for the treatment of glioblastoma. is creating a path for

In a study published in cell report medicineresearchers showed how a formulation of a compound called indirubin improved the survival of mice with malignant brain tumors.

They also tested new formulations that are easy to administer, bringing potential pharmaceutical approaches one step closer to clinical trials with human participants.

“What’s interesting about this drug is that it targets many key features of the disease,” said lead author Sean Lawler, associate professor of pathology and laboratory medicine at Brown University. increase. “This is attractive because this type of cancer continues to find ways to evade individual attack mechanisms.

The research team included scientists from Brown’s Legorreta Cancer Center and School of Engineering. Neurosurgery, Brigham and Women’s Hospital/Harvard Medical School. Phosphorex, Inc./Cytodigm, Inc.

Glioblastoma is the most common and aggressive brain tumor. Standard treatments are chemotherapy, radiation, and surgery, which may improve symptoms but do not cure or stop the cancer.

According to researchers, indirubin is a natural product found in indigo and is a constituent of Tangkei Ryukigan, a traditional Chinese herbal medicine that has been used to treat chronic myelogenous leukemia. Derivatives of indirubin have demonstrated cancer therapeutic potential through a variety of mechanisms.

A study published ten years ago by Lawler et al. showed that indirubin slowed the growth of glioblastoma tumors in mice. But researchers couldn’t explain why, he said. Additionally, the modified drug was not easy to work with, making it difficult for scientists to test dose levels and effectively deliver it to tumors.

Phosphorex, a Massachusetts-based biomedical company, contacted me as the scientists continued to study the compound. Phosphorex develops technologies to improve pharmaceutical formulations. Phosphorex has patented a formulation of indirubin called 6′-bromoindirubin acetoxime (BiA), making this compound more accessible as an injectable cancer treatment.

The researchers tested a nanoparticle formulation of BiA on glioblastoma tumors in mice, focusing on how the drug affects the immune system.

BiA not only slowed tumor cell growth and proliferation (confirming the results of previous studies), but also improved survival through its effects on key immunotherapeutic targets.

“This drug impacted the immune system in these mouse studies in ways that could enhance clinical immunotherapy in humans,” said Lawler, who is in charge of laboratory therapeutic approaches for the treatment of brain tumors. explained.

Researchers will continue testing the drug to see how it interacts with chemotherapy and radiation, with the goal of developing clinical trials for glioblastoma participants. Scientists have been studying glioblastoma for decades, but so far there haven’t been many significant therapeutic breakthroughs, according to Lawler.

“Over the past two decades or so, there have not been many notable discoveries that have had a meaningful impact on survival, so we are very keen to find new approaches,” said Lawler. “This research offers a new approach, which is why we are so excited.”

About this Brain Tumor Research News

author: press office
sauce: brown university
contact: Press Office – Brown University
image: image is public domain

Original research: open access.
“PPRX-1701, a nanoparticulate formulation of 6′-bromoindirubin acetoxime, has improved delivery and efficacy in a preclinical GBM model’ Mykola Zdioruk et al. cell report medicine

overview

PPRX-1701, a nanoparticulate formulation of 6′-bromoindirubin acetoxime, has improved delivery and efficacy in a preclinical GBM model

highlight

• PPRX-1701 is a deliverable formulation of 6-bromoindirubin-3′-acetoxime (BiA).
• Inhibits IDO1 expression and increases CD8 T cell infiltration in a GBM mouse model
• Data support investigation of this approach for potential future translations

summary

Derivatives of the herbal medicine indirubin have shown potential for cancer treatment through a variety of mechanisms. In this study, we investigated the effects of 6′-bromoindirubin-3′-acetoxime (BiA) on the immunosuppressive mechanisms of glioblastoma (GBM) and tested a BiA nanoparticle formulation, PPRX-1701, in an immunocompetent mouse model of GBM. Evaluate effectiveness.

Transcriptomic studies show that BiA regulates indoleamine 2,3-dioxygenase 1 (IDO1), a key enzyme in the tumor cell tryptophan-kynurenine-aryl hydrocarbon receptor (Trp-Kyn-AhR) immunosuppressive pathway. It was found to down-regulate immune-related genes, including BiA blocks IDO1 protein expression induced by interferon-γ (IFNγ) in vitro It also enhances T cell-mediated tumor cell killing in a GBM stem-like cell co-culture model. PPRX-1701 reaches intracranial murine GBM and significantly improves survival in an immunocompetent GBM model live.

Our results demonstrate that BiA improves survival in murine GBM models through its impact on key immunotherapeutic targets of GBM and can be efficiently delivered via PPRX-1701, a nanoparticle injectable formulation of BiA. is showing.