In vitro apoptosis in the human hepatoma cell line induced by transforming growth factor beta 1.
The effect of transforming growth factor beta 1 (TGF-beta 1) on human hepatoma cells (Hep 3B) was studied. Cell death was observed when the serum starved Hep 3B cells were exposed to a very low concentration of TGF-beta 1. The half-maximal cytocidal concentration of TGF-beta 1 was around 20 pM. Cell death began approximately 24 h following treatment, with more than 80% of the cells dying after 48 h. In contrast, the control cells, which were cultured in serum-free condition, still gradually proliferated. Furthermore, the cytocidal effect of TGF-beta 1 on Hep 3B cells was not altered by either cycloheximide or actinomycin D. It was discovered, using diphenylamine assay, that TGF-beta 1 induced DNA fragmentation in Hep 3B cells. Using gel electrophoresis, the fragmented DNA could be displayed, and showed a characteristic stepladder pattern. Thus, it appeared that TGF-beta 1 induced a particular pathway in Hep 3B cells in which de novo protein synthesis was not actively involved, but endogenous nuclease was activated which cleaves cellular DNA and induces cell death.
Lin
J K
JK
Department of Surgery, Veterans General Hospital, Taipei, Taiwan.
Chou
C K
CK
D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects*; D004249:DNA Damage; D006801:Humans; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000473:pathology*; D009707:Nucleosomes / Q000648:ultrastructure; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D009707:Nucleosomes; D016212:Transforming Growth Factor beta