Related Experiment Video
Updated: Sep 27, 2026
Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration
Published on: June 9, 2023
Molecular ordering of ROS production, mitochondrial changes, and caspase activation during sodium salicylate-induced
Young Mee Chung1, Yun Soo Bae, Soo Young Lee
1Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Womans University, Seoul, South Korea.
Abstract:
Salicylates and nonsteroidal anti-inflammatory drugs (NSAIDs) induce apoptosis in a variety of cancer cells, including those of colon, prostate, breast, and leukemia. We examined the effects of sodium salicylate (NaSal) on reactive oxygen species (ROS) production and the association of these effects with apoptotic tumor cell death. We demonstrate that NaSal mediates ROS production followed by a decrease in mitochondrial membrane potential (deltapsi(m)), release of cytochrome c, and activation of caspase-9 and caspase-3. However, expression of Bcl-2 or Bcl-x(L) prevents ROS production and subsequent loss of deltapsi(m), thereby inhibiting apoptotic cell death. The presence of ROS scavengers and an inhibitor of NADPH oxidase or expression of a dominant negative form of Rac1 blocks ROS production, deltapsi(m) collapse, and the subsequent activation of caspases. These observations indicate that NaSal mediates ROS production critical in the triggering of apoptotic tumor cell death through a Rac1-NADPH oxidase-dependent pathway. Our data collectively imply that NaSal-induced ROS are key mediators of deltapsi(m) collapse, which leads to the release of cytochrome c followed by caspase activation, culminating in tumor apoptosis.
Insights
Sodium salicylate (NaSal) triggers cancer cell death by increasing reactive oxygen species (ROS) through a Rac1-NADPH oxidase pathway. This process involves mitochondrial dysfunction and caspase activation, leading to apoptosis.
Area of Science:
- Molecular Biology
- Biochemistry
- Cancer Research
Background:
- Salicylates and NSAIDs are known to induce apoptosis in various cancer cells.
- The precise mechanisms underlying NSAID-induced apoptosis, particularly the role of reactive oxygen species (ROS), require further elucidation.
Purpose of the Study:
- To investigate the effects of sodium salicylate (NaSal) on reactive oxygen species (ROS) production in cancer cells.
- To determine the association between NaSal-mediated ROS production and apoptotic tumor cell death.
- To elucidate the specific molecular pathways involved in NaSal-induced apoptosis.
Main Methods:
- Treatment of cancer cells with sodium salicylate (NaSal).
- Measurement of reactive oxygen species (ROS) production.
- Assessment of mitochondrial membrane potential (Δψm) and cytochrome c release.
- Analysis of caspase-9 and caspase-3 activation.
- Investigation using ROS scavengers, NADPH oxidase inhibitors, and dominant-negative Rac1 expression.
Main Results:
- NaSal treatment induced ROS production, leading to a decrease in mitochondrial membrane potential (Δψm), cytochrome c release, and activation of caspase-9 and caspase-3.
- Expression of Bcl-2 or Bcl-xL inhibited NaSal-induced ROS production and subsequent apoptosis.
- ROS scavengers, NADPH oxidase inhibition, or dominant-negative Rac1 blocked ROS production, Δψm collapse, and caspase activation.
Conclusions:
- Sodium salicylate (NaSal) induces apoptotic tumor cell death through a pathway critically dependent on ROS production.
- The Rac1-NADPH oxidase pathway is essential for NaSal-mediated ROS generation.
- NaSal-induced ROS are key mediators of mitochondrial dysfunction, cytochrome c release, and caspase activation, culminating in apoptosis.
Related Concept Videos
01:24Caspases
01:22Cellular Injury V: Apoptosis and Autophagy
01:30Apoptosis