Accumulation of poly(adenosine diphosphate-ribose)by sustained supply of calcium inducing mitochondrial stress in pancreatic cancer cells  

作　　者：Keun-Yeong Jeong Jae Jun Sim Minhee Park Hwan Mook Kim 

机构地区：[1]Research and Development,Metimedi Pharmaceuticals,Incheon 22006,South Korea

出　　处：《World Journal of Gastroenterology》2022年第27期3422-3434,共13页世界胃肠病学杂志（英文版）

摘　　要：BACKGROUND 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 deprivation resulting in the caspase-independent death of cancer cells.AIM To investigate whether sustained calcium supply could induce an anticancer effect on pancreatic cancer by PAR accumulation.METHODS 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.RESULTS Mitochondrial ROS levels were elevated with increasing calcium influx into pancreatic cancer cells.Then,excess PAR accumulation,decreased PAR glycohydrolase and ADP-ribosyl hydrolase 3 levels,and energy deprivation were observed.In vitro and in vivo antitumor effects were confirmed to accompany elevated AIF levels.CONCLUSION 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.

关 键 词：Pancreatic cancer CALCIUM Reactive oxygen species Poly adenosine diphosphate-ribose Poly adenosine diphosphate-ribosylation Poly adenosine diphosphate-ribose polymerase Apoptosis-inducing factor Nicotinamide adenine dinucleotide Anticancer effect 

分 类 号：R735.9[医药卫生—肿瘤]