Hypericin inhibits choroidal endothelial cell proliferation and cord formation in vitro.
OBJECTIVE
To evaluate the effect of hypericin on bovine choroidal endothelial cell proliferation and cord formation and on protein kinase C activity.


METHODS
The effect of hypericin (0.1-5 microM) on bovine choroidal endothelial cell proliferation was determined by cell number counting and a 3H-thymidine uptake assay in media containing 1, 5 or 10% serum. For the cord formation assay, bovine choroidal endothelial cells were seeded on basement membrane matrix, and the lengths of the capillary-like structures (cords) formed were quantified by image analysis. The effect of hypericin on cord formation was evaluated in the presence of serum or vascular endothelial growth factor. The effect of hypericin on protein kinase C activity was also measured in the presence or absence of light.


RESULTS
Hypericin inhibited bovine choroidal endothelial cell proliferation in a dose-dependent manner in the presence of light but not in the dark. Serum dose-dependently masked the inhibition of DNA synthesis by hypericin. Cord formation by bovine choroidal endothelial cells was stimulated by serum or vascular endothelial growth factor and inhibited by hypericin in the presence of light. Protein kinase C activity was completely inhibited by hypericin in the presence of light but only mildly inhibited in the absence of light.


CONCLUSIONS
Hypericin inhibits bovine choroidal endothelial cell proliferation and cord formation and choroidal endothelial cell protein kinase C activity. These results suggest that hypericin should be further investigated in animal models for its potential to inhibit subretinal neovascularization.
Kimura
H
H
Doheny Eye Institute, University of Southern California School of Medicine, Los Angeles 90033, USA.
Harris
M S
MS
Sakamoto
T
T
Gopalakrishna
R
R
Gundimeda
U
U
Cui
J Z
JZ
Spee
C
C
Hinton
D R
DR
Ryan
S J
SJ
D000818:Animals; D000873:Anthracenes; D001485:Basement Membrane / Q000098:blood supply; D001769:Blood; D002417:Cattle; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002829:Choroid / Q000098:blood supply*; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008027:Light; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D000873:Anthracenes; D004791:Enzyme Inhibitors; D011838:Radiation-Sensitizing Agents; D010569:Perylene; C004965:hypericin; D004247:DNA; D011493:Protein Kinase C