title: Jungermannenone A and B induce ROS- and cell cycle-dependent apoptosis in prostate cancer cells in vitro.
abstract: OBJECTIVE
  Jungermannenone A and B (JA, JB) are new ent-kaurane diterpenoids isolated from Chinese liverwort Jungermannia fauriana, which show anti-proliferation activities in cancer cells. In this study we investigated the mechanisms underlying the anticancer action of JA and JB in PC3 human prostate cancer cells in vitro.
  
  
  METHODS
  A panel of 9 human cancer cell lines was tested. Cell proliferation was assessed with a real-time cell analyzer and MTT assay. Cell apoptosis, cell cycle distribution and ROS levels were measured using cytometry. Mitochondrial damage was examined by transmission electron microscopy. DNA damage was detected with comet assay. Apoptotic, DNA damage- and cell cycle-related proteins were analyzed using Western blotting. The expression of DNA repair genes was measured with qRT-PCR.
  
  
  RESULTS
  Both JA and JB exerted potent anti-proliferative action against the 9 cancer cell lines, and PC3 cells were more sensitive with IC50 values of 1.34±0.09 and 4.93±0.20 μmol/L, respectively. JA (1.5 μmol/L) and JB (5 μmol/L) induced PC3 cell apoptosis, which was attenuated by the caspase inhibitor Z-VAD. Furthermore, both JA and JB caused mitochondrial damage and ROS accumulation in PC3 cells, whereas vitamin C blocked the ROS accumulation and attenuated the cytotoxicity of JA and JB. Moreover, both JA and JB induced DNA damage, accompanied by downregulated DNA repair proteins Ku70/Ku80 and RDA51. JA induced marked cell cycle arrest at the G0/G1 phase, which was related to c-Myc suppression, whereas JB enforced the cell cycle blockade in the G2/M phase, which associated with activation of the JNK signaling.
  
  
  CONCLUSIONS
  Both JA and JB induce prostate cancer apoptosis via ROS accumulation and induction of cell cycle arrest.
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Ji-nan 250012, China.
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Guo
authors.affiliation: Department of Natural Product Chemistry, Shandong University School of Pharmaceutical Sciences, Ji-nan 250012, China.
authors.forename: Zhao-Min
authors.initials: ZM
authors.lastname: Lin
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Ji-nan 250012, China.
authors.forename: Mei-Juan
authors.initials: MJ
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Ji-nan 250012, China.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Dong
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Ji-nan 250012, China.
authors.forename: Huan-Min
authors.initials: HM
authors.lastname: Niu
authors.affiliation: Department of Urology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Charles Yf
authors.initials: CY
authors.lastname: Young
authors.affiliation: Department of Natural Product Chemistry, Shandong University School of Pharmaceutical Sciences, Ji-nan 250012, China.
authors.forename: Hong-Xiang
authors.initials: HX
authors.lastname: Lou
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Ji-nan 250012, China.
authors.forename: Hui-Qing
authors.initials: HQ
authors.lastname: Yuan
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D045786:Diterpenes, Kaurane / Q000737:chemistry* / Q000494:pharmacology*; D035926:Hepatophyta / Q000737:chemistry; D006801:Humans; D008297:Male; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D045786:Diterpenes, Kaurane; D017382:Reactive Oxygen Species