title: Andrographolide suppresses epithelial mesenchymal transition by inhibition of MAPK signalling pathway in lens epithelial cells.
abstract: Epithelial mesenchymal transition (EMT) of lens epithelial cells (LECs) may contribute to the development of posterior capsular opacification (PCO), which leads to visual impairment. Andrographolide has been shown to have therapeutic potential against various cancers. However, its effect on human LECs is still unknown. The purpose of this study is to evaluate the effect of andrographolide on EMT induced by growth factors in the fetal human lens epithelial cell line (FHL 124). Initially the LECs were treated with growth factors (TGF-beta 2 and bFGF) to induce EMT. Subsequently these EMT-induced cells were treated with andrographolide at 100 and 500 nM concentrations for 24 h. Our results showed that FHL 124 cells treated with growth factors had a significant decrease in protein and m-RNA levels of epithelial markers pax6 and E-Cadherin. After administering andrographolide, these levels significantly increased. It was noticed that EMT markers alpha-SMA, fibronectin and collagen IV significantly decreased after treatment with andrographolide when compared to the other group. Treatment with andrographolide significantly inhibited phosphorylation of ERK and JNK. Cell cycle analysis showed that andrographolide did not arrest cells at G0/G1 or G2/M at tested concentrations. Our findings suggest that andrographolide helps sustain epithelial characteristics by modulating EMT markers and inhibiting the mitogen-activated protein kinase (MAPK) signalling pathway in LECs. Hence it can prove to be useful in curbing EMT-mediated PCO.
authors.affiliation: Iladevi Cataract and IOL Research Centre, Gurukul road, Memnagar, Ahmedabad 380 052, India.
authors.forename: Forum
authors.initials: F
authors.lastname: Kayastha
authors.forename: Kaid
authors.initials: K
authors.lastname: Johar
authors.forename: Devarshi
authors.initials: D
authors.lastname: Gajjar
authors.forename: Anshul
authors.initials: A
authors.lastname: Arora
authors.forename: Hardik
authors.initials: H
authors.lastname: Madhu
authors.forename: Darshini
authors.initials: D
authors.lastname: Ganatra
authors.forename: Abhay
authors.initials: A
authors.lastname: Vasavada
mesh_terms: D000199:Actins / Q000378:metabolism; D002386:Cataract / Q000517:prevention & control*; D002460:Cell Line; D024141:Collagen Type IV / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004847:Epithelial Cells / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005353:Fibronectins / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D007908:Lens, Crystalline / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D024141:Collagen Type IV; D004224:Diterpenes; D005353:Fibronectins; D005419:Flavonoids; C030419:andrographolide; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one