Nuclear matrix associated protein PML: an arsenic trioxide apoptosis therapeutic target protein in HepG2 cells.
OBJECTIVE
To investigate arsenic trioxide (As(2)O(3))-induced apoptosis and the effects on cell nuclear matrix related protein promyelocytic leukaemia (PML).


METHODS
HepG2 cells were cultured in MEM medium and treated with 0.5, 2, 5 and 10 micro mol/L As(2)O(3) for either 24 h or 96 h at each concentration. In situ terminal deoxynucleotidyl transferase (TdT) labeling (TUNEL) and DNA ladders were used to detect apoptosis. Confocal microscopy and Western blotting were used to observe the expression of PML.


RESULTS
The growth rates of HepG2 cells were slower in the As(2)O(3) treated than the untreated control group. DNA ladder and TUNEL positive apoptotic cells could be detected in As(2)O(3) treated groups. The expression of PML decreased in HepG2 cells with 2 micro mol/L As(2)O(3) treatment. Confocal images demonstrated that the expression of PML protein in HepG2 cell nuclei decreased after treatment with 2 micro mol/L As(2)O(3), and micropunctates characteristic of PML protein in HepG2 cell nuclei disappeared after treatment with 5 micro mol/L As(2)O(3).


CONCLUSIONS
Our results show that arsenic trioxide can significantly inhibit the growth of HepG2 cells in vitro. As(2)O(3) induces apoptosis in HepG2 tumor cells in a time and concentration dependent manner. As(2)O(3) may degrade the PML protein in HepG2 cell nuclei. The decreased expression of PML in As(2)O(3) treated tumor cells is most likely to be caused by apoptosis. Nuclear matrix associated protein PML could be the target of As(2)O(3) therapy.
Yu
Ding
D
Department of Surgery, Shenzhen Hospital, Beijing University, Shenzhen 518036, China.
Wang
Zihui
Z
Zhu
Liyuan
L
Chew
E C
EC
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D015530:Nuclear Matrix / Q000187:drug effects* / Q000378:metabolism; D009687:Nuclear Proteins; D010087:Oxides / Q000494:pharmacology*; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D000970:Antineoplastic Agents; D001152:Arsenicals; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010087:Oxides; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D000077237:Arsenic Trioxide