PMID- 27749098
OWN - NLM
STAT- MEDLINE
DCOM- 20171016
LR  - 20181202
IS  - 1460-2202 (Electronic)
IS  - 0271-3683 (Linking)
VI  - 42
IP  - 4
DP  - 2017 Apr
TI  - Cytotoxic Effect of Latanoprost on Human Corneal Stromal Cells in vitro and its 
      Possible Mechanisms.
PG  - 534-541
LID - 10.1080/02713683.2016.1225770 [doi]
AB  - PURPOSE: To investigate the cytotoxic effect of latanoprost on corneal stroma and 
      its underlying cellular and molecular mechanisms using non-transfected human 
      corneal stromal (HCS) cells as an in vitro model. METHODS: After HCS cells were 
      treated with latanoprost at concentrations varying from 50 mg/l (clinical 
      therapeutic dosage) to 0.78125 mg/l, and cell morphology, cell viability, and 
      cell cycle were detected by light microscopy, methyl thiazolyl tetrazolium assay, 
      and flow cytometry (FCM) with propidium iodide (PI) staining, respectively. 
      Meanwhile, alterations in plasma membrane permeability, phosphatidylserine (PS) 
      orientation, DNA integrality, and cell ultrastructure were examined by acridine 
      orange (AO)/ethidium bromide (EB) double staining, FCM with Annexin-V/propidium 
      iodide (PI) staining, DNA electrophoresis, and transmission electron microscopy. 
      Furthermore, caspase activation, mitochondrial transmembrane potential (MTP), and 
      expression of pro-apoptotic regulators were determined by ELISA, FCM with 
      5,5',6,6'-tetrachloro-1,1',3,3'-tetraethybenzimida (JC-1) staining, and Western 
      blot, respectively. RESULTS: Latanoprost above concentrations of 3.125 mg/l can 
      induce dose- and time-dependent morphological abnormality, growth retardation, 
      viability decline, and plasma membrane permeability elevation of HCS cells. 
      Moreover, latanoprost can arrest the cell cycle of these cells at S phase and 
      induce PS externalization, DNA fragmentation, and apoptotic body formation of the 
      cells. Furthermore, latanoprost can induce activation of caspase-3, -8 and -9; 
      disruption of MTP; downregulation of anti-apoptotic Bcl-2; upregulation of 
      pro-apoptotic Bax; and cytoplasmic cytochrome c release. CONCLUSIONS: Latanoprost 
      above and at 3.125 mg/l (1/16 of its clinical therapeutic dosage) has a dose- and 
      time-dependent cytotoxicity to HCS cells by inducing death receptor-mediated 
      mitochondria-dependent apoptosis, which should be used with great caution in 
      clinical situations to avoid undesired damages to HCS cells.
FAU - Shen, Jun-Wei
AU  - Shen JW
AD  - a Laboratory for Corneal Tissue Engineering, College of Marine Life Sciences , 
      Ocean University of China , Qingdao , China.
FAU - Shan, Ming
AU  - Shan M
AD  - a Laboratory for Corneal Tissue Engineering, College of Marine Life Sciences , 
      Ocean University of China , Qingdao , China.
FAU - Peng, Yuan-Yuan
AU  - Peng YY
AD  - a Laboratory for Corneal Tissue Engineering, College of Marine Life Sciences , 
      Ocean University of China , Qingdao , China.
FAU - Fan, Ting-Jun
AU  - Fan TJ
AD  - a Laboratory for Corneal Tissue Engineering, College of Marine Life Sciences , 
      Ocean University of China , Qingdao , China.
LA  - eng
PT  - Journal Article
DEP - 20161017
PL  - England
TA  - Curr Eye Res
JT  - Current eye research
JID - 8104312
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Prostaglandins F, Synthetic)
RN  - 6Z5B6HVF6O (Latanoprost)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Antihypertensive Agents/*toxicity
MH  - Apoptosis/drug effects
MH  - Blotting, Western
MH  - Caspases/metabolism
MH  - Cell Cycle/drug effects
MH  - Cell Line
MH  - Cell Membrane Permeability/drug effects
MH  - Cell Survival/drug effects
MH  - Corneal Keratocytes/*drug effects/metabolism/pathology
MH  - Corneal Stroma/*drug effects/metabolism/pathology
MH  - DNA Fragmentation/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Humans
MH  - Latanoprost
MH  - Prostaglandins F, Synthetic/*toxicity
MH  - Time Factors
OTO - NOTNLM
OT  - Apoptosis
OT  - cytotoxicity
OT  - human corneal stromal cells
OT  - latanoprost
OT  - mitochondrion-dependent pathway
EDAT- 2016/10/18 06:00
MHDA- 2017/10/17 06:00
CRDT- 2016/10/18 06:00
PHST- 2016/10/18 06:00 [pubmed]
PHST- 2017/10/17 06:00 [medline]
PHST- 2016/10/18 06:00 [entrez]
AID - 10.1080/02713683.2016.1225770 [doi]
PST - ppublish
SO  - Curr Eye Res. 2017 Apr;42(4):534-541. doi: 10.1080/02713683.2016.1225770. Epub 
      2016 Oct 17.