Nitric oxide and calcium ions in apoptotic esophageal carcinoma cells induced by arsenite
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Updated: Sep 29, 2026

Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment
Published on: January 7, 2015
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
Aim:
To Quantitatively analyze the nitric oxide (NO) and Ca2+ in apoptosis of esophageal carcinoma cells induced by arsenic trioxide (As2O3).
Methods:
The cell line SHEEC1, a malignant esophageal epithelial cell induced by HPV in synergy with TPA in our laboratory, was cultured in a serum-free medium and treated with As2O3. Before and after administration of As2O3, NO production in cultured medium was detected quantitatively using the Griess Colorimetric method. Intracellular Ca2+ was labeled by using the fluorescent dye Fluo3-AM and detected under confocal laser scanning microscope (CLSM), which was able to acquire data in real-time enabling Ca2+ dynamics of individual cells in vitro. The apoptotic cells were examined under electron microscopy.
Results:
Intracellular concentration of Ca2+ increased from 1.00 units to 1.09-1.38 units of fluorescent intensity at As2O3 treatment and NO products subsequently released from As2O3-treated cells increased from 0.98-1.00 x10(-2)micromol x L(-1) up to 1.48-1.52 x10(-2)micromol x L(-1) and maintained in a high level continuously. Finally apoptosis of cells occurred,chromatin being agglutinated, cells shrunk,nuclei became round and mitochondria swelled.
Conclusion:
Ca2+ and NO increased with cell damage and apoptosis in cells treated by As2O3. The Ca2+ is an initial messenger to the apoptotic pathway. To investigate Ca2+ and NO will be a new direction for studying the apoptotic signaling messenger of the esophageal carcinoma cells induced by As2O3.
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.
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