Antidiabetic adiponectin receptor agonist AdipoRon suppresses tumour growth of pancreatic cancer by inducing RIPK1/ERK-dependent necroptosis
Year: 2018
Type: article
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.
Source: Cell Death and Disease
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,990
Awards: Effect of AdipoRon on the growth of pancreatic cancer cells in primary culture and obese prediabetic mice., Analysis of antitumor effects of adiponectin receptor agonists on pancreatic cancer, Two types of monoclonal antibodies generated by immunizing mice with MIA-PaCa-2 human pancreatic cancer cell line for diagnostic and therapeutic strategies for pancreatic cancer
OpenAlex ID: W2883103051