Format

Send to

Choose Destination
Cell Death Dis. 2018 Jul 23;9(8):804. doi: 10.1038/s41419-018-0851-z.

Antidiabetic adiponectin receptor agonist AdipoRon suppresses tumour growth of pancreatic cancer by inducing RIPK1/ERK-dependent necroptosis.

Author information

1
Department of Life Science, Shimane University Faculty of Medicine, 89-1 Ennya, Izumo, Shimane, 693-8501, Japan.
2
Department of Biochemistry, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.
3
Department of Pathology, Shimane University Faculty of Medicine, 89-1 Ennya, Izumo, Shimane, 693-8501, Japan.
4
Department of Digestive and General Surgery, Shimane University Faculty of Medicine, 89-1 Ennya, Izumo, Shimane, 693-8501, Japan.
5
Department of Life Science, Shimane University Faculty of Medicine, 89-1 Ennya, Izumo, Shimane, 693-8501, Japan. ktakenaga@chiba-cc.jp.
6
Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, 666-2 Nitona, Chiba, 260-8717, Japan. ktakenaga@chiba-cc.jp.

Abstract

The association between lower circulating adiponectin (APN) levels and the development of pancreatic cancer has been reported. However, the effect of APN on the growth and survival of pancreatic cancer cells remains elusive. Here, we investigate the effects of the anti-diabetic APN receptor (AdipoR) agonist AdipoRon and APN on human pancreatic cancer cells. We found that AdipoRon, but not APN, induces MIAPaCa-2 cell death, mainly through necroptosis. Mechanistically, although both AdipoRon and APN activate AMPK and p38 MAPK in an AdipoR-dependent manner that elicits survival signals, only AdipoRon induces rapid mitochondrial dysfunction through mitochondrial Ca2+ overload, followed by superoxide production via RIPK1 and ERK1/2 activation. Oral administration of AdipoRon suppresses MIAPaCa-2 tumour growth without severe adverse effects and kills cancer cells isolated from patients with pancreatic cancer. Thus, AdipoRon could be a therapeutic agent against pancreatic cancer as well as diabetes.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center