Additive antitumor effect of arsenic trioxide with exposure to ionizing radiation to human acute promyelocytic leukemia HL60 cells.
Oncol Rep
; 52(2)2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38963046
ABSTRACT
Arsenic trioxide (ATO) is expected to be a chemical drug with antitumor activity against acute promyelocytic leukemia (APL), a type of acute myeloid leukemia. In Japan, its antitumor effects were confirmed in clinical trials for APL, and it has been approved in various countries around the world. However, there have been no reports on ATO's antitumor effects on radioresistant leukemia cells, which can be developed during radiotherapy and in combination with therapeutic radiation beams. The present study sought to clarify the antitumor effect of ATO on APL cells with radiation resistance and determine its efficacy when combined with ionizing radiation (IR). The radiationresistant HL60 (ResHL60) cell line was generated by subjecting the native cells to 4Gy irradiation every week for 4 weeks. The halfmaximal inhibitory concentration (IC50) for cell proliferation by ATO on native cell was 0.87 µM (R2=0.67), while the IC50 for cell proliferation by ATO on ResHL60 was 2.24 µM (R2=0.91). IR exposure increased the subG1 and G2/M phase ratios in both cell lines. The addition of ATO resulted in a higher population of G2/M after 24 h rather than 48 h. When the rate of change in the subG1 phase was examined in greater detail, the subG1 phase in both control cells without ATO significantly increased by exposure to IR at 24 h, but only under the condition of 2 Gy irradiation, it had continued to increase at 48 h. ResHL60 supplemented with ATO showed a higher rate of subG1 change at 24 h; however, 2 Gy irradiation resulted in a decrease compared with the control. There was a significant increase in the ratio of the G2/M phase in cells after incubation with ATO for 24 h, and exposure to 2 Gy irradiation caused an even greater increase. To determine whether the inhibition of cell proliferation and cell cycle disruptions is related to reactive oxygen species (ROS) activity, intracellular ROS levels were measured with a flow cytometric assay. Although the ROS levels of ResHL60 were higher than those of native cells in the absence of irradiation, they did not change after 0.5 or 2 Gy irradiation. Furthermore, adding ATO to ResHL60 reduced intracellular ROS levels. These findings provide important information that radioresistant leukemia cells respond differently to the antitumor effect of ATO and the combined effect of IR.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Oxides
/
Arsenicals
/
Radiation, Ionizing
/
Leukemia, Promyelocytic, Acute
/
Cell Proliferation
/
Arsenic Trioxide
Limits:
Humans
Language:
En
Journal:
Oncol Rep
Journal subject:
NEOPLASIAS
Year:
2024
Type:
Article
Affiliation country:
Japan