Related Experiment Video

Updated: Jul 17, 2026

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
19:44

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

Role of Noxa in p53-independent fenretinide-induced apoptosis of neuroectodermal tumours

Jane L Armstrong1, Gareth J Veal, Christopher P F Redfern

  • 1Northern Institute for Cancer Research, School of Clinical and Laboratory Sciences, Newcastle University, Newcastle Upon Tyne, NE2 4HH, UK, J.L.Armstrong@ncl.ac.uk

Apoptosis : an International Journal on Programmed Cell Death
|January 12, 2007
PubMed

Insights

Fenretinide triggers cancer cell death via reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress, requiring the Noxa protein. This study highlights Noxa

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Death Pathways

Background:

  • Fenretinide induces apoptosis in neuroectodermal tumor cells through reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, and caspase activation.
  • The BH3-domain only protein Noxa is implicated in fenretinide-induced apoptosis, with its regulation by p53 being a key area of investigation.

Purpose of the Study:

  • To elucidate the role of the BH3-domain only protein Noxa in fenretinide-induced apoptosis of neuroectodermal tumor cells.
  • To investigate the regulatory mechanisms of Noxa expression and its relationship with p53 in response to various apoptotic stimuli.

Main Methods:

  • Utilized RNA interference (RNAi) to knockdown p53 and Noxa expression in neuroblastoma and melanoma cell lines.
  • Assessed Noxa expression, apoptosis, and protein levels in response to fenretinide, thapsigargin, cisplatin, and temozolomide.
  • Investigated the role of antioxidants and p53 in regulating Noxa induction and mediating apoptosis.

Main Results:

  • Fenretinide and thapsigargin induced Noxa expression independently of p53, and this induction was sensitive to antioxidants.
  • Noxa knockdown inhibited fenretinide- and thapsigargin-induced apoptosis, confirming Noxa's critical role in these pathways.
  • Conversely, p53 knockdown inhibited Noxa transcription and subsequent apoptosis induced by cisplatin or temozolomide, indicating a p53-dependent mechanism for these agents.

Conclusions:

  • Noxa induction is crucial for mediating apoptosis induced by fenretinide and thapsigargin, operating through a p53-independent pathway.
  • The study emphasizes the distinct roles of Noxa in both p53-dependent (cisplatin, temozolomide) and p53-independent (fenretinide, thapsigargin) apoptotic responses.
  • These findings highlight Noxa as a key determinant of apoptosis, with its regulation varying depending on the inducing agent and p53 status.

More Related Videos

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells09:37

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

Published on: August 25, 2021

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...
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...
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.
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
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...