Effect of reversine on cell cycle, apoptosis, and activation of hepatic stellate cells

Experimental and clinical evidence show that liver fibrosis is potentially reversible. Hepatic stellate cells (HSCs) play a key role in the development of liver fibrosis. Some studies have shown that reversine could induce cell apoptosis. We attempted to elucidate the effect of reversine on cell cycle, apoptosis, and activation of HSCs. Data showed that reversine induced morphological changes in HSCs, inhibited cell proliferation, and induced cell-cycle arrest at the G2/M phase. Reversine induced cell apoptosis through caspase-dependent and mitochondria-dependent pathways. Reversine inhibited the activation of HSCs through TGF-beta signaling pathway and degraded extracellular matrix protein collagen-I. The decreased TIMP1 and TGF-beta(1) proteins promoted fibrosis reversion. Reversine might be a promising drug for liver fibrosis reversion because it induces HSCs apoptosis, restrains cell proliferation, reduces HSCs activation, and degrades extracellular matrix in vitro.