Nitric oxide and calcium ions in apoptotic esophageal carcinoma cells induced by arsenite

Zhong-Ying Shen1, Wen-Ying Shen, Ming-Hua Chen

  • 1Department of Pathology, Medical College of Shantou University, 22 Xinling Road, Shantou 515031, Guandong Province, China. zhongyingshen@yahoo.com

Abstract

Insights

Arsenic trioxide (As2O3) induces apoptosis in esophageal carcinoma cells by increasing intracellular calcium (Ca2+) and nitric oxide (NO). Ca2+ acts as an initial messenger in this apoptotic pathway, offering new research directions.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Esophageal carcinoma is a significant global health concern.
  • Arsenic trioxide (As2O3) is a chemotherapeutic agent with known cytotoxic effects.
  • Understanding the molecular mechanisms of As2O3-induced apoptosis is crucial for treatment optimization.

Purpose of the Study:

  • To quantitatively analyze the roles of nitric oxide (NO) and calcium ions (Ca2+) in As2O3-induced apoptosis of esophageal carcinoma cells.
  • To elucidate the signaling pathway involving Ca2+ and NO in As2O3-treated esophageal cancer cells.

Main Methods:

  • Cultured SHEEC1 esophageal carcinoma cells were treated with As2O3.
  • Nitric oxide (NO) production was measured using the Griess Colorimetric method.
  • Intracellular Ca2+ dynamics were assessed using the fluorescent dye Fluo3-AM and confocal laser scanning microscopy (CLSM).
  • Apoptosis was examined via electron microscopy.

Main Results:

  • As2O3 treatment led to a significant increase in intracellular Ca2+ levels.
  • A subsequent rise in NO production was observed in As2O3-treated cells.
  • Morphological changes indicative of apoptosis, including chromatin agglutination and mitochondrial swelling, were confirmed.

Conclusions:

  • Both Ca2+ and NO levels increase during As2O3-induced cell damage and apoptosis.
  • Ca2+ appears to function as an initial messenger in the apoptotic signaling pathway.
  • Investigating Ca2+ and NO offers a novel approach to understanding As2O3-mediated apoptosis in esophageal carcinoma.

Related Concept Videos

Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure to...
Cellular Injury IV: Necrosis01:16

Cellular Injury IV: Necrosis

Necrosis is a form of irreversible cell death caused by severe injury such as ischemia, toxins, or trauma. Unlike programmed cell death, it is an uncontrolled, pathological process that typically provokes inflammation in surrounding tissues.Pathophysiologic ChangesNecrosis begins when cells sustain critical damage, leading to swelling of organelles, particularly mitochondria, and rapid ATP depletion. As energy levels decline, membrane ion pumps fail, leading to calcium influx and eventually,...