Related Experiment Video

Updated: Aug 19, 2026

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
13:22

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Published on: October 23, 2019

Imatinib mesylate (STI571) interference with growth of neuroectodermal tumour cell lines does not critically involve

Geertuy Te Kronnie1, Fabio Timeus, Andrea Rinaldi

  • 1Department of Pediatrics, University of Padova, 35128 Padova, Italy.

International Journal of Molecular Medicine
|August 4, 2004
PubMed

Insights

STI571 (imatinib mesylate) effectively inhibits neuroectodermal tumor growth by reducing cell proliferation and increasing apoptosis. This therapeutic agent shows promise for treating c-Kit positive neuroectodermal tumors, independent of direct c-Kit pathway inhibition.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Neuroectodermal tumors, including Ewing sarcoma (ES), primitive neuroectodermal tumors (PNET), and neuroblastoma (NB), are often associated with c-Kit expression.
  • STI571 (imatinib mesylate) is a tyrosine kinase inhibitor with a known therapeutic role in certain cancers, and its potential in c-Kit positive neuroectodermal tumors was hypothesized.

Purpose of the Study:

  • To evaluate the efficacy of STI571 in inhibiting the proliferation of c-Kit positive neuroectodermal tumor cell lines in vitro.
  • To assess the anti-tumor effects of STI571 in a mouse model of Ewing sarcoma.
  • To elucidate the molecular mechanisms underlying STI571's action in these tumor models.

Main Methods:

  • In vitro assays using eleven neuroectodermal tumor cell lines (ES, PNET, NB) treated with varying concentrations and durations of STI571.
  • Microphysiometer cytosensor analysis to measure cellular metabolic rates and assess global protein phosphorylation via immunoprecipitation and ELISA.
  • Apoptosis assessment using flow cytometry (propidium iodide, Annexin V) and caspase-3 activity assays, alongside microarray analysis for gene expression.
  • In vivo studies in nude mice with ES-derived tumors, analyzing tumor volume, histology, and apoptotic gene expression post-STI571 treatment.

Main Results:

  • STI571 demonstrated a concentration- and time-dependent decrease in tumor cell proliferation and a corresponding increase in apoptosis.
  • Metabolic activity and global protein phosphorylation were reduced by STI571 in a dose- and time-dependent manner, suggesting a broad impact beyond c-Kit.
  • Tumor volume in STI571-treated mice was significantly reduced compared to controls; apoptosis appeared independent of caspase activation and linked to reactive oxygen species (ROS) accumulation.

Conclusions:

  • STI571 exhibits significant anti-proliferative and pro-apoptotic effects on neuroectodermal tumor cells, both in vitro and in vivo.
  • The therapeutic efficacy of STI571 in these models is observed despite the inhibition appearing, at least partially, independent of direct c-Kit signaling.
  • The findings support the potential of STI571 as a therapeutic agent for neuroectodermal tumors, with a mechanism possibly involving ROS-mediated cell death.

More Related Videos

Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor07:21

Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor

Published on: May 2, 2022

Comet Assay to Quantify DNA Damage in FLT3 Mutant-expressing 32D Cells after Exposure to Type I and Type II FLT3 Inhibitors04:36

Comet Assay to Quantify DNA Damage in FLT3 Mutant-expressing 32D Cells after Exposure to Type I and Type II FLT3 Inhibitors

Published on: October 17, 2025

Related Concept Videos

Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...