Related Experiment Video

Updated: Feb 18, 2026

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
06:00

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

Published on: May 14, 2016

11.6K

The sirtuin 1/2 inhibitor tenovin-1 induces a nonlinear apoptosis-inducing factor-dependent cell death in a p53 null

Christian Marx1, Lisa Marx-Blümel2,3, Nora Lindig2,3

  • 1Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany.

Investigational New Drugs
|November 19, 2017
PubMed

Insights

Tenovin-1, a sirtuin 1/2 inhibitor, triggers distinct cell death pathways in Ewing sarcoma. It induces caspase-mediated death in p53 wild-type cells and caspase-independent death, with a unique bell-shaped response, in p53 null cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Sirtuin 1/2 inhibitor tenovin-1 activates p53, showing potential in cancer management.
  • Ewing sarcoma is a pediatric bone cancer with limited treatment options.

Purpose of the Study:

  • To investigate the response of Ewing sarcoma cells to tenovin-1.
  • To compare tenovin-1's effects in p53 wild-type versus p53 null Ewing sarcoma cells.

Main Methods:

  • Flow cytometry for cell death, mitochondrial membrane potential, and reactive oxygen species (ROS).
  • Caspase 3/7 activity assays, mRNA expression profiling, and immunoblotting.
  • Assessment of tenovin-1's dose-response effects in different p53 contexts.

Main Results:

  • Tenovin-1 induced caspase-mediated cell death in p53 wild-type Ewing sarcoma cells.
  • In p53 null cells, tenovin-1 triggered caspase-independent cell death via apoptosis-inducing factor.
  • A nonlinear, bell-shaped dose-response pattern was observed in p53 null cells, with lower concentrations being more effective.

Conclusions:

  • Tenovin-1 activates distinct cell death mechanisms dependent on p53 status in Ewing sarcoma.
  • The study reveals a novel bell-shaped concentration response for tenovin-1 in p53 null cells.
  • Findings offer new insights into tenovin-1's mechanism of action and potential therapeutic applications in cancer.
Keywords:
Apoptosis-inducing factor (AIF)Ewing’s sarcomaNonlinear responseSirtuinsTenovin-1p53

More Related Videos

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen19:44

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Published on: May 30, 2012

19.2K
Yeast As a Chassis for Developing Functional Assays to Study Human P5314:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

10.1K

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
8.8K
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...
5.3K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.6K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
8.8K
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
4.5K
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.2K