title: Andrographolide reduces proliferation and migration of lens epithelial cells by modulating PI3K/Akt pathway.
abstract: Lens epithelial cell proliferation, migration, and transdifferentiation are involved in the development of subcapsular cataracts and postoperative capsular opacification (PCO). PI3K/Akt pathway is involved in the proliferation and migration of lens epithelial cells. Andrographolide is the main bioactive component of Andrographis paniculata and is known to possess anti-proliferative and anti-migratory activities. The purpose of this study is to evaluate the effect of andrographolide on proliferation and migration induced by growth factors (TGF-β and bFGF) in the lens epithelial cell line, FHL 124. We have also evaluated the role of the PI3K/Akt pathway and its alteration by andrographolide during proliferation and migration of lens epithelial cells. The results showed that andrographolide significantly inhibited proliferation in a dose and time dependent manner. The growth factors, TGF-β and bFGF, induced migration of lens epithelial cells, which was lowered by andrographolide. The growth factors also up regulated phosphorylated Akt (Ser473) and Akt (Thr308), which was abolished by simultaneous treatment of andrographolide. Similar changes were also observed with the PI3K inhibitor, LY290042. Our findings suggest that andrographolide reduces proliferation, migration, and phosphorylated Akt levels in lens epithelial cells. Hence andrographolide can be utilized for the prevention of PCO.
authors.affiliation: Iladevi Cataract and IOL Research Centre, Gurukul Road, Memnagar, Ahmedabad, 380052, India.
authors.forename: Forum
authors.initials: F
authors.lastname: Kayastha
authors.affiliation: Iladevi Cataract and IOL Research Centre, Gurukul Road, Memnagar, Ahmedabad, 380052, India.
authors.forename: Hardik
authors.initials: H
authors.lastname: Madhu
authors.affiliation: Iladevi Cataract and IOL Research Centre, Gurukul Road, Memnagar, Ahmedabad, 380052, India.
authors.forename: Abhay
authors.initials: A
authors.lastname: Vasavada
authors.affiliation: Iladevi Cataract and IOL Research Centre, Gurukul Road, Memnagar, Ahmedabad, 380052, India. Electronic address: kaidjohar@icirc.in.
authors.forename: Kaid
authors.initials: K
authors.lastname: Johar
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007211:Indoles / Q000378:metabolism; D007908:Lens, Crystalline / Q000166:cytology / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001973:Bromodeoxyuridine; D002867:Chromones; D004224:Diterpenes; D004791:Enzyme Inhibitors; D007211:Indoles; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C030419:andrographolide; C007293:DAPI
keywords: Andrographolide; Cell migration; Cell proliferation; Lens epithelial cells; PI3K/Akt signaling; TGF-β; bFGF