title: Cinobufagin inhibits tumor growth by inducing intrinsic apoptosis through AKT signaling pathway in human nonsmall cell lung cancer cells.
abstract: The cinobufagin (CB) has a broad spectrum of cytotoxicity to inhibit cell proliferation of various human cancer cell lines, but the molecular mechanisms still remain elusive. Here we observed that CB inhibited the cell proliferation and tumor growth, but induced cell cycle arrest and apoptosis in a dose-dependent manner in non-small cell lung cancer (NSCLC) cells. Treatment with CB significantly increased the reactive oxygen species but decreased the mitochondrial membrane potential in NSCLC cells. These effects were markedly blocked when the cells were pretreated with N-acetylcysteine, a specific reactive oxygen species inhibitor. Furthermore, treatment with CB induced the expression of BAX but reduced that of BCL-2, BCL-XL and MCL-1, leading to an activation of caspase-3, chromatin condensation and DNA degradation in order to induce programmed cell death in NSCLC cells. In addition, treatment with CB reduced the expressions of p-AKTT308 and p-AKTS473 and inhibited the AKT/mTOR signaling pathway in NSCLC cells in a time-dependent manner. Our results suggest that CB inhibits tumor growth by inducing intrinsic apoptosis through the AKT signaling pathway in NSCLC cells.
authors.affiliation: Department of Thoracic Surgery, Second Hospital of Jilin University, Changchun, P.R. China.
authors.forename: Guangxin
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.|Department of Integrative Endemic Area, Tongji Hospital of Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pathology, Second Hospital of Jilin University, Changchun, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Thoracic Surgery, Second Hospital of Jilin University, Changchun, P.R. China.
authors.forename: Jindong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Second Hospital of Jilin University, Changchun, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Second Hospital of Jilin University, Changchun, P.R. China.
authors.forename: Chengyan
authors.initials: C
authors.lastname: Jin
authors.affiliation: Department of Thoracic Surgery, Second Hospital of Jilin University, Changchun, P.R. China.
authors.forename: Peiyan
authors.initials: P
authors.lastname: Hua
authors.affiliation: Department of Thoracic Surgery, Second Hospital of Jilin University, Changchun, P.R. China.
authors.forename: Ge
authors.initials: G
authors.lastname: Song
authors.affiliation: Department of Thoracic Surgery, Second Hospital of Jilin University, Changchun, P.R. China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Lisa L H
authors.initials: LL
authors.lastname: Nguyen
authors.affiliation: Jilin Provincial Key Laboratory on Molecular and Chemical Genetic, Second Hospital of Jilin University, Changchun, P.R. China.
authors.forename: Ranji
authors.initials: R
authors.lastname: Cui
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Runhua
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Lizhong
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Second Hospital of Jilin University, Changchun, P.R. China.
authors.forename: Xingyi
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002018:Bufanolides / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002018:Bufanolides; D051057:Proto-Oncogene Proteins c-akt; C002471:cinobufagin
keywords: apoptosis; cinobufagin; mitochondrial transmembrane potential; non-small cell lung cancer; reactive oxygen species