Related Experiment Video

Updated: Jan 29, 2026

Biochemical Assays for Analyzing Activities of ATP-dependent Chromatin Remodeling Enzymes
10:14

Biochemical Assays for Analyzing Activities of ATP-dependent Chromatin Remodeling Enzymes

Published on: October 25, 2014

15.2K

Small Molecule Cocktail DLC79 Suppresses Gliomagenesis by Activating Ascl1 and Remodeling Transcriptome

Chuxiao Mao1,2, Zhancheng Deng1, Zhuming Chen1,3

  • 1Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China.

Cells
|January 28, 2026
PubMed

Insights

Researchers developed a small-molecule cocktail that reprograms glioblastoma cells into neuron-like cells. This pharmacological reprogramming approach inhibits glioma malignancy and reduces tumor growth, offering a novel therapeutic strategy.

Area of Science:

  • Neuro-oncology
  • Pharmacological reprogramming
  • Cancer therapy

Background:

  • Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis due to invasive growth and treatment resistance.
  • While genetic reprogramming of glioma cells exists, pharmacological reprogramming presents a more clinically translatable approach.

Purpose of the Study:

  • To identify a pharmacological method for reprogramming human glioma cells into a less malignant phenotype.
  • To evaluate the efficacy of this reprogramming strategy in vitro and in vivo.

Main Methods:

  • Phenotype-driven screening identified a multi-target small-molecule cocktail (DLC79) comprising DAPT, LDN193189, CHIR99021, I-BET762, and Isx9.
  • DLC79's effect on glioma cell identity, transcriptional landscape, and oncogenic properties was assessed.
  • In vitro assays measured proliferation, migration, invasion, and clonogenicity.
  • A subcutaneous xenograft model evaluated tumor growth and bioluminescence after DLC79 pretreatment.

Main Results:

  • DLC79 effectively reprogrammed human glioma cells into neuron-like cells, activating endogenous ASCL1 and remodeling the transcriptional landscape.
  • Neuronal markers (MAP2, GAD67) were upregulated, while glial markers were suppressed.
  • DLC79 treatment inhibited glioma cell proliferation, migration, invasion, and clonogenicity in vitro.
  • In vivo, DLC79 pretreatment reduced tumor bioluminescence by 56% and tumor mass by 47%.

Conclusions:

  • Pharmacological reprogramming using DLC79 is a viable strategy to convert malignant glioma cells into a less oncogenic, neuron-like state.
  • This approach demonstrates significant anti-glioma activity, suggesting a novel therapeutic paradigm for glioblastoma.
Keywords:
Ascl1glioblastomapharmacological reprogrammingsmall moleculestumorigenicity suppression

More Related Videos

Human In Vitro Suppression as Screening Tool for the Recognition of an Early State of Immune Imbalance14:01

Human In Vitro Suppression as Screening Tool for the Recognition of an Early State of Immune Imbalance

Published on: July 22, 2011

15.0K
The Measurement and Treatment of Suppression in Amblyopia08:34

The Measurement and Treatment of Suppression in Amblyopia

Published on: December 14, 2012

50.6K

Related Concept Videos

Nucleosome Remodeling02:54

Nucleosome Remodeling

Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
11.1K
Bone Remodeling01:40

Bone Remodeling

Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
40.4K
Osteoclasts in Bone Remodeling01:31

Osteoclasts in Bone Remodeling

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
4.1K
Molecules and Compounds02:38

Molecules and Compounds

Atoms and Molecules
68.6K
Prokaryotic Transcriptional Activators and Repressors01:58

Prokaryotic Transcriptional Activators and Repressors

The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
Transcription of prokaryotic...
25.4K
Activation Energy01:26

Activation Energy

Activation energy is the minimum amount of energy necessary for a chemical reaction to move forward. The higher the activation energy, the slower the rate of the reaction. However, adding heat to the reaction will increase the rate, since it causes molecules to move faster and increase the likelihood that molecules will collide. The collision and breaking of bonds represents the uphill phase of a reaction and generates the transition state. The transition state is an unstable high-energy state...
86.6K