Homoisoflavanone inhibits retinal neovascularization through cell cycle arrest with decrease of cdc2 expression.
Neovascularization in the eye is the most common cause of blindness in all age groups; retinopathy of prematurity (ROP), diabetic retinopathy, and age-related macular degeneration. Despite current advances in surgical treatments, ROP remains as the most serious problem of vision loss in children. Here, we report that homoisoflavanone, a natural product from Cremastra appendiculata, significantly reduces retinal neovascularization in a mouse model of ROP. Homoisoflavanone inhibited the cell growth of HUVECs, but its cytotoxic effect was not observed in a concentration range of 1-20 microM. HUVECs population gradually increased in G2/M phase and reduced in G0/G1 and S phases after exposure to the compound. Homoisoflavanone decreased the level of cdc2 expression whereas the level of p21WAF1 expression was increased in a dose-dependent manner. These data demonstrate that homoisoflavanone could inhibit retinal neovascularization and be applied in the treatment of other vasoproliferative retinopathies.
Kim
Jeong Hun
JH
Department of Ophthalmology, College of Medicine, Seoul National University, and Seoul Artificial Eye Center Clinical Research Institute, Seoul National University Hospital, Seoul 110-744, Republic of Korea.
Kim
Ki Hyun
KH
Kim
Jin Hyoung
JH
Yu
Young Suk
YS
Kim
Young-Myeong
YM
Kim
Kyu-Won
KW
Kwon
Ho Jeong
HJ
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D007529:Isoflavones / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D012178:Retinopathy of Prematurity / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology