title: Genistein inhibits cell growth and induces apoptosis through up-regulation of miR-34a in pancreatic cancer cells.
abstract: Pancreatic cancer (PC) is the fourth most common cause of cancer-related deaths in the United States, suggesting that designing novel therapeutic strategy is required to improve the survival outcome of patients diagnosed with PC. Recently, microRNAs (miRNA) have been found to be involved in the regulation of multiple aspects of tumor development and progression including PC. In this study, we investigate whether miR-34a plays a critical role in the control of cell growth and apoptosis in PC cells. We found that Re-expression (forced expression) of miR-34a inhibits cell growth and induces apoptosis, with concomitant down-regulation of Notch-1 signaling pathway, one of the target of miR-34a. Moreover, treatment of PC cells with a natural compound genistein led to the up-regulation of miR-34a, resulting in the down-regulation of Notch-1, which was correlated with inhibition of cell growth, and induction of apoptosis. Our findings suggest that genistein could function as a non-toxic activator of a miRNA that can suppress the proliferation of PC cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui, PR China, 233030.
authors.forename: Jun
authors.initials: J
authors.lastname: Xia
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Duan
authors.forename: Aamir
authors.initials: A
authors.lastname: Ahmad
authors.forename: Bin
authors.initials: B
authors.lastname: Bao
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Banerjee
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.forename: Jia
authors.initials: J
authors.lastname: Ma
authors.forename: Jian
authors.initials: J
authors.lastname: Geng
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Chen
authors.forename: K M Wahidur
authors.initials: KM
authors.lastname: Rahman
authors.forename: Lucio
authors.initials: L
authors.lastname: Miele
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods; D019833:Genistein / Q000494:pharmacology / Q000627:therapeutic use*; D006131:Growth Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D051881:Receptor, Notch1 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D016588:Anticarcinogenic Agents; D006131:Growth Inhibitors; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D019833:Genistein