Rhein Induces a Necrosis-Apoptosis Switch in Pancreatic Acinar Cells

Abstract EN

Objectives.

The Chinese herbal medicine Da-Cheng-Qi decoction can regulate a necrosis-apoptosis switch in injured pancreatic acinar cells.

This study investigated the effects of rhein, a component of this medicine, on a necrosis-apoptosis switch in pancreatic rat AR42J cells.

Methods.

Cerulein-treated AR42J cells were used.

After pretreatment with 479, 119.8, or 29.9 μg/L rhein, cells were cocultured with rhein and cerulein (10−8 M) for 4, 8, or 16 h.

Apoptosis and necrosis were examined using annexin V and propidium iodide costaining.

Mitochondria-dependent apoptosis-associated proteins were examined using enzyme-linked immunosorbent assays and western blotting.

Results.

Few cells died in untreated samples.

The number was significantly higher in 16-h-cerulein-treated samples and treatment with 479 μg/L rhein most effectively increased the apoptotic-to-necrotic cell ratio ( P < 0.05 ).

In cerulein-treated cells, rhein increased the concentrations of p53, cytochrome C, and caspase-3, and increased the Bax/Bcl-2 ratio in a time- and dose-dependent manner, with the maximum effect in cells treated with 479 μg/L rhein for 16 h ( P < 0.05 ).

Conclusions.

Rhein induces the necrosis-apoptosis switch in injured pancreatic acinar cells in a time- and dose-dependent manner.

Mitochondria-dependent apoptosis signaling pathways might play an important role in this effect.