The inherent cellular level of reactive oxygen species: one of the mechanisms determining apoptotic susceptibility of leukemic cells to arsenic trioxide.
Though reactive oxygen species (ROS) has been noticed to be involved in arsenic trioxide (As(2)O(3))-induced apoptosis of tumor cells, its role in apoptosis signaling remained to be elucidated. The objective of this work was to explore the association of the inherent cellular ROS level with the susceptibility of the tumor cells to apoptosis induction by As(2)O(3). Low concentration of As(2)O(3) was administered to cultured leukemic cell lines NB4, U937, HL60 and K562. The difference in apoptotic sensitivity was displayed among four cell types. ROS probes were incubated with the cells in the absence of As(2)O(3), and ROS was thus quantified relatively by flow cytometry. We manifested, in four cell types, the inherently existed difference in whole ROS quantity, and a positive correlation between the inherent ROS level and their apoptotic sensitivity to As(2)O(3). Furthermore, by interference using a ROS producer, we demonstrated that an elevation of ROS level would sensitize the cells to As(2)O(3)-induced apoptosis. The results of the present work suggested that the inherent ROS level might be determinative in tumor cells for their apoptotic susceptibility to As(2)O(3).
Yi
J
J
Department of Cell Biology, Shanghai Second Medical University, Shanghai 200025, People's Republic of China.
Gao
F
F
Shi
G
G
Li
H
H
Wang
Z
Z
Shi
X
X
Tang
X
X
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D007951:Leukemia, Myeloid / Q000378:metabolism* / Q000473:pathology; D009285:Naphthoquinones / Q000494:pharmacology; D010087:Oxides / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001152:Arsenicals; D009285:Naphthoquinones; D010087:Oxides; D017382:Reactive Oxygen Species; C063002:2,3-dimethoxy-1,4-naphthoquinone; D000077237:Arsenic Trioxide