Related Experiment Video

Updated: Jun 28, 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

[Regulation of arsenic trioxide-inducing apoptosis]

X Huang1

  • 1Institute of Hematology, Peoples' Hospital, Beijing Medical University, Beijing 100044.

Zhonghua Xue Ye Xue Za Zhi = Zhonghua Xueyexue Zazhi
|October 17, 2001
PubMed
Abstract

Insights

Arsenic trioxide (As2O3) induces apoptosis by interacting with intracellular thiol (-SH) groups and activating caspases. Retinoic acid (RA) effects on As2O3-induced apoptosis vary by cell type.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Apoptosis is a critical cellular process involved in development and disease.
  • Arsenic trioxide (As2O3) is a chemotherapeutic agent known to induce apoptosis.
  • The precise mechanisms of As2O3-induced apoptosis, including the roles of intracellular thiols and caspases, require further elucidation.

Purpose of the Study:

  • To investigate the interplay between intracellular thiol (-SH) groups, caspases, retinoic acid (RA), and As2O3-induced apoptosis.
  • To determine the influence of thiol compounds and caspase inhibitors on As2O3-induced apoptosis in leukemia cell lines.
  • To examine the synergistic or antagonistic effects of RA in combination with As2O3 on apoptosis.

Main Methods:

  • In vitro studies were conducted using NB4 and HL-60 leukemia cell lines.
  • The effects of N-acetylcysteine (NAC), buthionine sulfoximine (BSO), and other thiol compounds on As2O3-induced apoptosis were assessed.
  • Caspase inhibitors, including Z-VAD.fmk and Y-VAD.fmk, were used to probe caspase activation pathways.
  • The combined effects of retinoic acid (RA) and As2O3 on apoptosis were evaluated in different cell types.

Main Results:

  • N-acetylcysteine (NAC) completely inhibited As2O3-induced apoptosis, while buthionine sulfoximine (BSO) potentiated it; other thiols had no significant effect.
  • The broad-spectrum caspase inhibitor Z-VAD.fmk blocked As2O3-induced apoptosis, whereas the caspase-3 inhibitor Y-VAD.fmk did not.
  • Retinoic acid (RA) exhibited synergistic effects with As2O3 in HL-60 cells but antagonistic effects in NB4 cells.

Conclusions:

  • As2O3 induces apoptosis by binding to intracellular thiol (-SH) groups, altering signal transduction pathways, and selectively activating caspases.
  • The modulatory effect of retinoic acid (RA) on As2O3-induced apoptosis is cell-type dependent, highlighting the complexity of apoptotic regulation.

More Related Videos

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

In Vitro Scratch Assay to Demonstrate Effects of Arsenic on Skin Cell Migration09:24

In Vitro Scratch Assay to Demonstrate Effects of Arsenic on Skin Cell Migration

Published on: February 23, 2019

Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
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...
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...
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...