Iodine125 seed radiation induces ROSmediated apoptosis, autophagy and paraptosis in human esophageal squamous cell carcinoma cells.
Oncol Rep
; 43(6): 2028-2044, 2020 06.
Article
in En
| MEDLINE
| ID: mdl-32323828
ABSTRACT
Iodine125 (125I) seed brachytherapy has been proven to be a safe and effective treatment for advanced esophageal cancer; however, the mechanisms underlying its actions are not completely understood. In the present study, the anticancer mechanisms of 125I seed radiation in human esophageal squamous cell carcinoma (ESCC) cells (Eca109 and KYSE150) were determined, with a particular focus on the mode of cell death. The results showed that 125I seed radiation significantly inhibited cell proliferation, and induced DNA damage and G2/M cell cycle arrest in both ESCC cell lines. 125I seed radiation induced cell death through both apoptosis and paraptosis. Eca109 cells were primarily killed by inducing caspasedependent apoptosis, with 6 Gy radiation resulting in the largest response. KYSE150 cells were primarily killed by inducing paraptosis, which is characterized by extensive cytoplasmic vacuolation. 125I seed radiation induced autophagic flux in both ESCC cell lines, and autophagy inhibition by 3methyladenine enhanced radiosensitivity. Furthermore 125I seed radiation induced increased production of reactive oxygen species (ROS) in both ESCC cell lines. Treatment with an ROS scavenger significantly attenuated the effects of 125I seed radiation on endoplasmic reticulum stress, autophagy, apoptosis, paraptotic vacuoles and reduced cell viability. In vivo experiments showed that 125I seed brachytherapy induced ROS generation, initiated cell apoptosis and potential paraptosis, and inhibited cell proliferation and tumor growth. In summary, the results demonstrate that in ESCC cells, 125I seed radiation induces cell death through both apoptosis and paraptosis; and at the same time initiates protective autophagy. Additionally, 125I seed radiationinduced apoptosis, paraptosis and autophagy was considerably mediated by ROS.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Esophageal Neoplasms
/
Reactive Oxygen Species
/
Esophageal Squamous Cell Carcinoma
/
Iodine Radioisotopes
Type of study:
Clinical_trials
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Oncol Rep
Journal subject:
NEOPLASIAS
Year:
2020
Document type:
Article