title: Autophagy Induced by CX-4945, a Casein Kinase 2 Inhibitor, Enhances Apoptosis in Pancreatic Cancer Cell Lines.
abstract: Pancreatic cancer is the most lethal malignancy with only a few effective chemotherapeutic drugs. Because the inhibition of casein kinase 2 (CK2) has been reported as a novel therapeutic strategy for many cancers, we investigated the effects of CK2 inhibitors in pancreatic cancer cell lines.
  
  
  
  The BxPC3, 8902, MIA PaCa-2 human pancreatic cancer cell lines, and CX-4945, a novel CK2 inhibitor, were used. Autophagy was analyzed by acridine orange staining, fluorescence microscope detection of punctuate patterns of GFP-tagged LC3 and immunoblotting for LC3. Cell survival, cell cycle, and apoptosis analysis was performed.
  
  
  
  CX-4945 induced significant inhibition of proliferation and triggered autophagy in pancreatic cancer cells. This suppression of proliferation was caused by the direct inhibition of CK2α, which was required for autophagy and apoptosis in pancreatic cancer cells. CX-4945 suppressed cell cycle progression in G2/M and induced apoptosis. The inhibition of CX-4945-induced autophagy was rescued by 3-methyladenine or small interfering RNA against Atg7, which attenuated apoptosis in pancreatic cancer cells.
  
  
  
  CX-4945, a potent and selective inhibitor of CK2, effectively induces autophagy and apoptosis in pancreatic cancer cells, indicating that the induction of autophagy by CX-4945 may have an important role in the treatment of pancreatic cancer.
authors.affiliation: From the Division of Hepatobiliary and Pancreatic Surgery, Departments of *Surgery and †Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine; ‡Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine; and §Department of Oncology and ∥Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Dae Wook
authors.initials: DW
authors.lastname: Hwang
authors.forename: Kwang Sup
authors.initials: KS
authors.lastname: So
authors.forename: Song Cheol
authors.initials: SC
authors.lastname: Kim
authors.forename: Kwang-Min
authors.initials: KM
authors.lastname: Park
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Lee
authors.forename: Sun-Whe
authors.initials: SW
authors.lastname: Kim
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Choi
authors.forename: Jin Kyung
authors.initials: JK
authors.lastname: Rho
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Choi
authors.forename: Jae Cheol
authors.initials: JC
authors.lastname: Lee
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D009287:Naphthyridines / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010619:Phenazines; D034622:RNA Interference
chemical_list: D009287:Naphthyridines; D010619:Phenazines; C025946:3-methyladenine; C555142:silmitasertib; D047390:Casein Kinase II; D000225:Adenine