title: Novel ferrocenyl derivatives exert anti-cancer effect in human lung cancer cells in vitro via inducing G1-phase arrest and senescence.
abstract: OBJECTIVE
  To investigate the effects of 7 novel 1-ferrocenyl-2-(5-phenyl-1H-1,2,4-triazol-3-ylthio) ethanone derivatives on human lung cancer cells in vitro and to determine the mechanisms of action.
  
  
  METHODS
  A549 human lung cancer cells were examined. Cell viability was analyzed with MTT assay. Cell apoptosis and senescence were examined using Hoechst 33258 and senescence-associated-β-galactosidase (SA-β-gal) staining, respectively. LDH release was measured using a detection kit. Cell cycle was analyzed using a flow cytometer. Intracellular ROS level was measured with the 2',7'-dichlorodihydrofluorescein probe. Phosphorylation of p38 was determined using Western blot.
  
  
  RESULTS
  Compounds 5b, 5d, and 5e (40 and 80 μmol/L) caused significant decrease of A549 cell viability, while other 4 compounds had no effect on the cells. Compounds 5b, 5d, and 5e (80 μmol/L) induced G1-phase arrest (increased the G1 population by 22.6%, 24.23%, and 26.53%, respectively), and markedly increased SA-β-gal-positive cells. However, the compounds did not cause nuclear DNA fragmentation and chromatin condensation in A549 cells. Nor did they affect the release of LDH from the cells. The compounds significantly elevated the intracellular ROS level, decreased the mitochondrial membrane potential, and increased p38 phosphorylation in the cells. In the presence of the antioxidant and free radical scavenger N-acetyl-L-cysteine (10 mmol/L), above effects of compounds 5b, 5d, and 5e were abolished.
  
  
  CONCLUSIONS
  The compounds 5b, 5d, and 5e cause neither apoptosis nor necrosis of A549 cells, but exert anti-cancer effect via inducing G1-phase arrest and senescence through ROS/p38 MAP-kinase pathway.
authors: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Institute of Developmental Biology, School of Life Science, Shandong University, Ji-nan, China.
authors: Ying
authors: Y
authors: Li
authors: Han-lin
authors: HL
authors: Ma
authors: Lei
authors: L
authors: Han
authors: Wei-yong
authors: WY
authors: Liu
authors: Bao-xiang
authors: BX
authors: Zhao
authors: Shang-li
authors: SL
authors: Zhang
authors: Jun-ying
authors: JY
authors: Miao
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D016922:Cellular Senescence / Q000187:drug effects* / Q000502:physiology; D005296:Ferrous Compounds / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D000075163:Metallocenes; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D005296:Ferrous Compounds; D000075163:Metallocenes; D017382:Reactive Oxygen Species; C004998:ferrocene
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