Bcl-2 blocks apoptotic signal of transforming growth factor-β in human hepatoma cells

Transforming growth factor-β (TGF-β) has been shown to induce apoptosis on normal hepatocytes and hepatoma cells both in vitro and in vivo. However, how the TGF-β induces apoptosis is still not clear. We examined the expression of anti-apoptosis proteins and sensitivity to TGF-β in three well differentiated human hepatoma cell lines. Two TGF-β sensitive cell lines Hep3B and HuH7 totally lacked Bcl-2. In contrast, the TGF-β resistant HepG2 cells expressed a substantial amount of Bcl-2. All three cell lines expressed equal amounts of Bcl-X(L), Bcl-X(s) and Bax. Overexpression of Bcl-2 in Hep3B and HuH7 cells protected them from TGF-β-induced apoptosis. TGF-β treatment increased intracellular peroxide production and suppressed the expression of glutathione-S-transferase in the Hep3B cells, and these effects were partially suppressed by the overexpression of Bcl-2. These results suggest that Bcl-2 may protect cell from TGF-β-F-induced apoptosis by interfering TGF-β generated signals leading to induce reactive oxygen species production.