The cell cycle related apoptotic susceptibility to arsenic trioxide is associated with the level of reactive oxygen species.
Double staining flow cytometry was performed using 7-amino actinomycin D and 6-carboxy-2', 7'-dichlorodihydrofluorescein diacetate, to detect the level fluctuation of reactive oxygen species (ROS) during the cell cycle of normal NB4 cells. Our results showed that NB4 cells possessed higher level of ROS in G2/M phase than in G1 and S phases. Double staining flow cytometry, with TdT mediated dUTP nick end labeling (Tunel) and propidium iodide (PI), indicated that As2O3 (2 microM) could induce apoptosis in NB4 cells prevailingly from G2/M phase, and this efficacy was enhanced upon co-administration of 2, 3-dimethoxy-1, 4-naphthoquinone (DMNQ) (2.5 microM) which could produce the endogenous ROS. These results suggested that different ROS level in different cell cycle phases of NB4 cells might determine the selective induction of G2/M apoptosis and the cells' susceptibility to apoptosis by As2O3.
Gao
Fei
F
Department of Cell Biology, Shanghai Second Medical University, Shanghai 200025, China.
Yi
Jing
J
Yuan
Jing Qi
JQ
Shi
Gui Ying
GY
Tang
Xue Ming
XM
D000111:Acetylcysteine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D003609:Dactinomycin / Q000031:analogs & derivatives* / Q000737:chemistry; D005434:Flow Cytometry; D005452:Fluoresceins / Q000737:chemistry; D006801:Humans; D020287:In Situ Nick-End Labeling; D007399:Interphase / Q000187:drug effects / Q000502:physiology; D009285:Naphthoquinones / Q000494:pharmacology; D010087:Oxides / Q000494:pharmacology*; D011419:Propidium / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000970:Antineoplastic Agents; D001152:Arsenicals; D005452:Fluoresceins; D009285:Naphthoquinones; D010087:Oxides; D017382:Reactive Oxygen Species; C082546:6'-carboxyl-2',7'-dichlorodihydrofluorescein; D003609:Dactinomycin; D011419:Propidium; C063002:2,3-dimethoxy-1,4-naphthoquinone; C025942:7-aminoactinomycin D; D002374:Catalase; D000077237:Arsenic Trioxide; D000111:Acetylcysteine