The effect of arsenic trioxide on the expression of Hsc and HNF4 in nuclear matrix proteins in HepG2 cells.
Anticancer agents interfere with the proliferation and survival of tumor cells by a variety of mechanisms. An important factor in the development of a cytotoxic effect by certain anticancer agents is the localization of drug-induced lesions within the cell nucleus. Drug-target interactions at the level of nuclear matrix (NM) may be critical events in the induction of cell death by some of these agents. Arsenic trioxide (As2O3) was identified as a very potent anti-leukemic agent by inducing apoptosis. The present study shows that As2O3 significantly inhibits the growth of hepatoblastoma cell line, HepG2, changes the composition of nuclear matrix proteins and reduces the expression of Hsc 70 and HNF4 in HepG2, which in turn initiate a cascade of events that compromise multiple nuclear functions and, ultimately, cell survival.
Yu
D
D
Department of Surgery, Shenzhen Central Hospital, China.
Wang
Z H
ZH
Cheng
S B
SB
Li
H K
HK
Chan
H B
HB
Chew
E C
EC
D034961:Antigens, Nuclear; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D006131:Growth Inhibitors / Q000494:pharmacology; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015530:Nuclear Matrix / Q000187:drug effects* / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis*; D010087:Oxides / Q000494:pharmacology*; D010750:Phosphoproteins / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D034961:Antigens, Nuclear; D000970:Antineoplastic Agents; D001152:Arsenicals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D051557:Hepatocyte Nuclear Factor 4; C403128:MLX protein, human; D009687:Nuclear Proteins; D010087:Oxides; D010750:Phosphoproteins; D014157:Transcription Factors; D000077237:Arsenic Trioxide