Related Experiment Video

Updated: Apr 15, 2026

In Vivo Model for Testing Effect of Hypoxia on Tumor Metastasis
12:03

In Vivo Model for Testing Effect of Hypoxia on Tumor Metastasis

Published on: December 9, 2016

13.0K

RETRA exerts anticancer activity in Ewing's sarcoma cells independent of their TP53 status

Jürgen Sonnemann1, Désirée Grauel1, Lisa Blümel1

  • 1Department of Paediatric Haematology and Oncology, Children's Clinic, Jena University Hospital, Jena, Germany.

European Journal of Cancer (Oxford, England : 1990)
|March 25, 2015
PubMed

Insights

The small-molecule RETRA effectively suppresses Ewing

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Mutant p53 protein can promote cancer by inhibiting p73.
  • The small molecule RETRA disrupts this interaction and has shown anticancer effects in carcinoma cells with mutant p53.
  • Previous studies indicated RETRA's activity was limited to mutant p53-bearing cells.

Purpose of the Study:

  • To investigate the effectiveness of RETRA in Ewing's sarcoma (ES) cells with varying TP53 statuses (mutant, null, and wild-type).
  • To compare RETRA's efficacy in ES cells with its known activity in carcinoma cells.
  • To elucidate the mechanism of RETRA's action in ES cells, independent of TP53 status.

Main Methods:

  • Testing RETRA's efficacy on three mutant p53, two p53 wild-type, and p53-null Ewing's sarcoma cell lines.
  • Assessing RETRA-induced apoptosis via flow cytometry (mitochondrial depolarization, DNA fragmentation), caspase 3/7 activity assays, and PARP-1 cleavage.
  • Analyzing G2/M cell cycle arrest and the expression of p53 target genes (PUMA, p21) in response to RETRA, irrespective of TP53 status.

Main Results:

  • RETRA demonstrated efficacy in all tested Ewing's sarcoma cell lines, including those with mutant, null, and wild-type TP53.
  • Apoptosis and G2/M cell cycle arrest were induced by RETRA independently of the TP53 cellular status.
  • RETRA induced p53 target gene expression (PUMA, p21) in ES cells regardless of their TP53 status, unlike its limited effect in other cancer cell types.

Conclusions:

  • RETRA exhibits broad efficacy against Ewing's sarcoma cells, irrespective of their TP53 mutational status.
  • The mechanism of action involves apoptosis induction and cell cycle arrest, independent of TP53.
  • These findings support further in vivo investigation of RETRA as a potential therapeutic agent for Ewing's sarcoma.
Keywords:
ApoptosisCancer therapyCell cycleEwing’s sarcomaGene expressionRETRAp53p73

More Related Videos

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

11.7K
An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells08:54

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells

Published on: July 20, 2014

14.6K

Related Concept Videos

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...
5.5K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.1K
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...
9.2K
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...
8.5K
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...
6.2K