title: Latcripin-13 domain induces apoptosis and cell cycle arrest at the G1 phase in human lung carcinoma A549 cells.
abstract: Latcripin-13 domain, isolated from the transcriptome of Lentinula edodes C91-3, contains a regulator of chromosome condensation (RCC1) domain/β-lactamase-inhibitor protein II (BLIP-II) and a plant homeodomain (PHD). Latcripin-13 domain has been shown to have antitumor effects. However, the underlying molecular pharmacology is largely unknown. We report here that Latcripin-13 domain induced cell cycle arrest in the G1 phase and caused the apoptosis of human lung carcinoma A549 cells via the GSK3β-cyclin D1 and caspase-8/NF-κB signaling pathways. Western blot analysis showed that Latcripin-13 domain decreased cyclin D1 and cyclin-dependent kinase 4 (CDK4), while it increased the ratio of GSK3β/phosphorylated GSK3β. Importantly, Latcripin-13 domain induced nuclear fragmentation and chromatin condensation in the A549 cells. In addition, treatment of the A549 cells with Latcripin-13 domain resulted in the loss of mitochondrial membrane potential, accompanied by an increase in the Bax/Bcl-2 ratio and activation of caspase-3, -8, and -9. Intriguingly, western blot analysis revealed that NF-κB was significantly downregulated by Latcripin-13 domain. These results demonstrated that Latcripin-13 domain induced apoptosis and cell cycle arrest at G1 phase in the A549 cells, providing a mechanism for the antitumor effects of Latcripin-13 domain.
authors.affiliation: Department of Critical Care Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116021, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Critical Care Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116021, P.R. China.
authors.forename: Xianyao
authors.initials: X
authors.lastname: Wan
authors.affiliation: Department of Microbiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Microbiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Mintao
authors.initials: M
authors.lastname: Zhong
authors.affiliation: Department of Microbiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Sha
authors.affiliation: Department of Microbiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Ben
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Microbiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Microbiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Ruan
authors.affiliation: Department of Microbiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Microbiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D002843:Chromatin / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics; D053938:DNA Fragmentation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005656:Fungal Proteins / Q000502:physiology*; D016193:G1 Phase / Q000187:drug effects*; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016328:NF-kappa B / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002843:Chromatin; D005656:Fungal Proteins; C000595217:Latcripin-13 protein, Lentinula edodes; D016328:NF-kappa B; D019938:Cyclin D1; D000071679:Glycogen Synthase Kinase 3 beta; D053181:Caspase 8