[Mechanism of arsenic trioxide-induced apoptosis in hepatic blastoma cells HepG2].
OBJECTIVE
To investigate the mechanism of arsenic trioxide (As(2)O(3)) induced apoptosis in hepatic blastoma cells HepG2 and its effects on cell nuclear matrix related protein promyelocytic leukaemia (PML).


METHODS
HepG2 cells were cultured in MEM medium and treated with different concentrations of As(2)O(3) for either 24 h or 96 h. In situ terminal deoxynucleotidyl transferase (TdT) labeling (TUNEL) and DNA ladder were applied to detect apoptosis. Confocal microscopy and western blot were performed to observe the expression of PML.


RESULTS
TUNEL positive apoptotic cells and DNA ladder 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), and micropunctates characteristic of PML protein in HepG2 cell nuclei almost disappeared after the treatment of 5 micro mol/L As(2)O(3).


CONCLUSIONS
As(2)O(3) induces HepG2 tumor cell apoptosis in a time- and concentration-dependent manner. As(2)O(3) may degradate the PML protein in HepG2 cell nuclei. The decreased expression of PML is closely correlated with 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
Zi-hui
ZH
Zhu
Li-yuan
LY
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D056945:Hep G2 Cells; D018197:Hepatoblastoma / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D009687:Nuclear Proteins / Q000032:analysis; D010087:Oxides / Q000494:pharmacology*; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis
D000970:Antineoplastic Agents; D001152:Arsenicals; D009687:Nuclear Proteins; D010087:Oxides; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D000077237:Arsenic Trioxide