SM22α inhibits cell proliferation and protects against anticancer drugs and γ-radiation in HepG2 cells: Involvement of metallothioneins

Smooth muscle protein 22-alpha (SM22α) has been postulated to affect the structure and function of the actin filament. In this study, we report on the significant induction of SM22α by cytotoxic agents in HepG2 cells. SM22α-overexpression inhibited the activation of IGF-1Rβ/Akt and Erk, consequently suppressing cell proliferation. On the other hand, SM22α-overexpressing cells became resistant to apoptotic cell death caused by cytotoxic agents, in which metallothionein (MT) isoforms, especially MT1G, were significantly induced. MT1G-overexpression also conferred cellular resistance, and SM22α regulated the expression of MT1G at a transcriptional level. This study provides the first demonstration of SM22α-induced blockage of cell proliferation and cellular resistance to overcome the detrimental effects of damaging agents.