Synergistic effect of cell differential agent-II and arsenic trioxide on induction of cell cycle arrest and apoptosis in hepatoma cells.
OBJECTIVE
To illustrate the possible role of cell differential agent-II (CDA-II) in the apoptosis of hepatoma cells induced by arsenic trioxide (As(2)O(3)).


METHODS
Hepatoma cell lines BEL-7402 and HepG2 were treated with As(2)O(3) together with CDA-II. Cell surviving fraction was determined by MTT assay; morphological changes were observed by immunofluorescence staining of Hoechst 33,258; and cell cycle and the apoptosis index were determined by flow cytometry (FCM).


RESULTS
Cytotoxicity of CDA-II was low. Nevertheless, CDA-II could strongly potentiate arsenic trioxide-induced apoptosis. At 1.0 g/L CDA-II, IC(50) of As(2)O(3) in hepatoma cell lines was reduced from 5.0 micromol/L to 1.0 micromol/L (P<0.01). The potentiation of apoptosis was dependent on the dosage of CDA-II. FCM indicated that in hepatoma, cell growth was inhibited by CDA-II at lower concentrations (<2.0 g/L) primarily by arresting at S and G(2) phase, and at higher concentrations (>2.0 g/L) apoptotic cell and cell cycle arresting at G(1) phase increased proportionally. The combination of two drugs led to much higher apoptotic rates, as compared with the either drug used alone.


CONCLUSIONS
CDA-II can strongly potentiate As(2)O(3)-induced apoptosis in hepatoma cells, and two drugs can produce a significant synergic effect.
Liu
Jian-Wei
JW
Department of General Surgery, Guangzhou Red Cross Hospital, Jinan University, Guangzhou 510220, Guangdong Province, China. mabeliu@public.guangzhou.gd.cn
Tang
Yi
Y
Shen
Yan
Y
Zhong
Xue-Yun
XY
D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D002470:Cell Survival; D005434:Flow Cytometry; D006131:Growth Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D001152:Arsenicals; D006131:Growth Inhibitors; D010087:Oxides; D000077237:Arsenic Trioxide