title: A novel bispidinone analog induces S‑phase cell cycle arrest and apoptosis in HeLa human cervical carcinoma cells.
abstract: 2,4,6,8-(3)-Tetranitrophenyl-3,7-diazabicyclo[3.3.1]nonan-9-one (B16), a bispidinone analog, was synthesized to investigate its effects on cell viability, the cell cycle, and apoptotic pathways in HeLa human cervical cancer cells. B16 decreased the percentage of viable cells in WST-8 assays, and morphological changes associated with apoptotic cell death were observed, including cell shrinkage and disruption. Annexin V-FITC/PI dual staining assays showed that B16 significantly increased the early apoptosis of HeLa cells after 24 h of treatment. Moreover, DNA content analysis and [3H]-thymidine incorporation assays showed that B16 induced S-phase cell cycle arrest and inhibited DNA replication after 24 h of treatment. Following treatment with 25 µM of B16, an increase in reactive oxygen species and a decrease in mitochondrial membrane potential were observed by flow cytometry. In addition, the expression levels of caspase cascade and Bcl-2 family proteins determined by western blotting suggested that the induction of apoptosis by B16 was associated with a caspase- and mitochondrial-dependent pathway in HeLa cells. In conclusion, B16 induced early apoptosis and S-phase cell cycle arrest in HeLa cells via a caspase- and mitochondrial‑dependent pathway.
authors.affiliation: Department of Chemistry and Institute of Basic Sciences, Inje University, Gimhae 621-749, Republic of Korea.
authors.forename: Xu
authors.initials: X
authors.lastname: Yi
authors.affiliation: Department of Chemistry and Institute of Basic Sciences, Inje University, Gimhae 621-749, Republic of Korea.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Institute of Basic Sciences, Inje University, Gimhae 621-749, Republic of Korea.
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Jeong
authors.affiliation: Department of Chemistry and Institute of Basic Sciences, Inje University, Gimhae 621-749, Republic of Korea.
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Shin
authors.affiliation: Department of Chemistry and Institute of Basic Sciences, Inje University, Gimhae 621-749, Republic of Korea.
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Park
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P.R. China.
authors.forename: Song
authors.initials: S
authors.lastname: You
authors.affiliation: Department of Chemistry and Institute of Basic Sciences, Inje University, Gimhae 621-749, Republic of Korea.
authors.forename: Dong-Kyoo
authors.initials: DK
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001372:Aza Compounds / Q000737:chemistry / Q000494:pharmacology; D053961:Azabicyclo Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D020169:Caspases / Q000096:biosynthesis; D045744:Cell Line, Tumor; D004261:DNA Replication / Q000187:drug effects; D005260:Female; D006367:HeLa Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D009578:Nitrobenzenes / Q000138:chemical synthesis / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
chemical_list: C000603031:2,4,6,8-(3)-tetranitrophenyl-3,7-diazabicyclo(3.3.1)nonan-9-one; D001372:Aza Compounds; D053961:Azabicyclo Compounds; D009578:Nitrobenzenes; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C011758:3,7-diazabicyclo(3.3.1)nonane; D020169:Caspases