Published online Jul 21, 2022. doi: 10.3748/wjg.v28.i27.3422
Peer-review started: January 11, 2022
First decision: March 8, 2022
Revised: March 15, 2022
Accepted: June 26, 2022
Article in press: June 26, 2022
Published online: July 21, 2022
Processing time: 188 Days and 4 Hours
The biochemical phenomenon defined as poly adenosine diphosphate (ADP)-ribosylation (PARylation) is essential for the progression of pancreatic cancer. However, the excessive accumulation of poly ADP-ribose (PAR) induces apoptosis-inducing factor (AIF) release from mitochondria and energy depri
To investigate whether sustained calcium supply could induce an anticancer effect on pancreatic cancer by PAR accumulation.
Two pancreatic cancer cell lines, AsPC-1 and CFPAC-1 were used for the study. Calcium influx and mitochondrial reactive oxygen species (ROS) were observed by fluorescence staining. Changes in enzyme levels, as well as PAR accumulation and energy metabolism, were measured using assay kits. AIF-dependent cell death was investigated followed by confirming in vivo anticancer effects by sustained calcium administration.
Mitochondrial ROS levels were elevated with increasing calcium influx into pancreatic cancer cells. Then, excess PAR accumulation, decreased PAR glyco
This study visualized the potential anticancer effects of excessive PAR accumulation by sustained calcium supply on pancreatic cancer, however elucidating a clear mode of action remains a challenge, and it should be accompanied by further studies to assess its potential for clinical application.
Core Tip: Accumulation of poly adenosine diphosphate-ribose (PAR) was induced by an increase in reactive oxygen species following sustained calcium supply, which in turn led to the death of pancreatic cancer cells by energy deprivation and apoptosis-inducing factor expression. Although calcium-mediated accumulation of PAR would be a potential strategy for the treatment of pancreatic cancer, the association with the mechanical role of calcium in enabling the inactivation of PAR-degrading enzymes needs to be elucidated.