Rhein Induces a Necrosis‐Apoptosis Switch in Pancreatic Acinar Cells

Abstract

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.

Rhein, a novel Histone Deacetylase (HDAC) inhibitor with antifibrotic potency in human myocardial fibrosis

“…Although p53 was multiply predicted as robust upstream regulator throughout all conditions, TP53 mRNA levels were not affected in any experimental group. However surprisingly, the presence of Rhein under normoxic conditions increased p53 protein levels, in line with other reports 27,28,37 . Collectively, these findings pointed towards a posttranslational effect of Rhein on p53, leading to its increased abundance and transcriptional activity.…”

“…Consistently, both secretome and transcriptome analyses commonly identified p53 as confident affected upstream regulator. This finding supports already published work, showing the interaction between Rhein and p53 27,28 , collectively proving the functionality of Rhein and its action in the presently applied system. Furthermore, computational analysis also predicted CDKN1A (p21) as potential candidate, an imminent downstream target of p53 and known key regulator of proliferation and cell cycle 29,30 .…”

Protective Role of Selenium on Aflatoxin B1-Induced Hepatic Dysfunction and Apoptosis of Liver in Ducklings

“…To measure concentrations of Bcl-2, Bax, caspase-3, and p53, the duck ELISA kits (Shanghai Yanji Bioengineering Company, China) described in previous studies were used [15,16]. Liver tissues were prepared following the manufacturer's instructions.…”

Current trends in pharmacological approaches for treatment and management of acute pancreatitis – a review

“…In-vitro rat pancreatic acinar cells Experimental AP animal models Rhein promoted dose-dependent enhancement of the ratio of apoptotic-to necrotic cells, the level of cytochrome C, caspase-3, p53 and Bax/Bcl-2 ratio indicating the ability to channel the mitochondrial apoptosis of injured cells rather than necrosis thus reducing the effects of AP [112,113] Conjugated HPDM-rhein compound reduced the AP severity which was indicated by lower amylase, lower levels of IL-6 and TNF-a in plasma, lung and pancreas 12. Rutin decreased the pancreatic injury indicated by less necrosis, infiltration, oedema, and lower serum levels of the pancreatic enzymes and also increased apoptosis [114][115][116] Rutin reduced inflammation via several mechanisms such as decreased expression of various cytokines like TNF-a, IL-1b, IL-6 and decreased neutrophil infiltration AP, acute pancreatitis; PACs, pancreatic acinar cells; ROS, reactive oxygen species; SAP, severe acute pancreatitis; SOD, superoxide dismutase.…”