Apoptosis susceptibility of tumor cells to arsenic trioxide and the inherent cellular level of reactive oxygen species.
OBJECTIVE
To explore the association of inherent cellular reactive oxygen species (ROS) levels with susceptibility of the tumor cells to apoptosis induction by arsenic trioxide (As(2)O(3)).


METHODS
Low concentration (2 micromol/L) of As(2)O(3) was administered to two cultured leukemic cell lines, NB4 and U937, and two esophageal carcinoma cell lines, EC1.71 (also named EC/CUHK1) and EC1867, to confirm the difference in apoptosis susceptibility of NB4 versus U937 and of EC1.71 versus EC1867. Dihydrogenrhodamine 123 (DHR123), used as a ROS capture agent, was incubated with cells in the absence of As(2)O(3). Fluorescence intensity of rhodamine 123, the product of cellular oxidation of DHR123, was detected by flow cytometry and ROS was measured.


RESULTS
Low concentration of As(2)O(3) induced apoptosis was more likely to occur in NB4 and EC1.71 cells than in U937 and EC1867 cells, or NB4 was more sensitive than U937, and EC1.71 more sensitive than EC1867 to As(2)O(3). The inherent cellular ROS level is higher in NB4 than in U937, and also higher in EC1.71 than in EC1867.


CONCLUSIONS
The difference in cellular ROS level is positively associated with cellular susceptibility to apoptosis induction by As(2)O(3). The inherent ROS level might be important in defining apoptotic susceptibility to As(2)O(3).
Laboratory of Cell Biology, Shanghai Second Medical University, Shanghai 200025, China. yijing@shsmu.edu.cn
Jing
J
Yi
Fei
F
Gao
Guiying
G
Shi
Hui
H
Li
Xuegeng
X
Shi
Xueming
X
Tang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000235:genetics; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D010087:Oxides / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020112:Rhodamine 123; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D001152:Arsenicals; D004273:DNA, Neoplasm; D005456:Fluorescent Dyes; D010087:Oxides; D017382:Reactive Oxygen Species; D020112:Rhodamine 123; D000077237:Arsenic Trioxide