Accumulation of poly(adenosine diphosphate-ribose)by sustained supply of calcium inducing mitochondrial stress in pancreatic cancer cells
作者机构：Research and DevelopmentMetimedi PharmaceuticalsIncheon 22006South Korea
出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)
年 卷 期：2022年第28卷第27期
页 面：3422-3434页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
主 题：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
摘 要：BACKGROUND The biochemical phenomenon defined as poly adenosine diphosphate(ADP)-ribosylation(PARylation)is essential for the progression of pancreatic ***,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 *** To investigate whether sustained calcium supply could induce an anticancer effect on pancreatic cancer by PAR *** Two pancreatic cancer cell lines,AsPC-1 and CFPAC-1 were used for the *** influx and mitochondrial reactive oxygen species(ROS)were observed by fluorescence *** in enzyme levels,as well as PAR accumulation and energy metabolism,were measured using assay ***-dependent cell death was investigated followed by confirming in vivo anticancer effects by sustained calcium *** Mitochondrial ROS levels were elevated with increasing calcium influx into pancreatic cancer ***,excess PAR accumulation,decreased PAR glycohydrolase and ADP-ribosyl hydrolase 3 levels,and energy deprivation were *** vitro and in vivo antitumor effects were confirmed to accompany elevated AIF *** 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.
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