Elsevier

Experimental Eye Research

Volume 128, November 2014, Pages 23-26
Experimental Eye Research

Short communication
Andrographolide reduces proliferation and migration of lens epithelial cells by modulating PI3K/Akt pathway

https://doi.org/10.1016/j.exer.2014.09.002Get rights and content

Highlights

  • Andrographolide attenuates proliferation and migration induced by TGF-β2 and bFGF.

  • Andrographolide down-regulates phosphorylated Akt.

  • Andrographolide could be implicated for prevention of PCO.

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.

Section snippets

Acknowledgments

Forum Kayastha is the recipient of the INSPIRE Fellowship (IF110617) and is thankful to the Department of Science and Technology (DST), New Delhi, INDIA. The authors would like to thank Darshini Ganatra for cell culture assistance and Dr. Devarshi Gajjar for helpful comments on the manuscript.

References (41)

  • H.L. Chandler et al.

    Prevention of posterior capsular opacification through cyclooxygenase-2 inhibition

    Mol. Vis.

    (2007)
  • H.L. Chandler et al.

    The effect of phosphorylated Akt inhibition on posterior capsule opacification in an ex vivo canine model

    Mol. Vis.

    (2010)
  • L.J. Dawes et al.

    TGFbeta/Smad4-dependent and -independent regulation of human lens epithelial cells

    Investig. Ophthalmol. Vis. Sci.

    (2009)
  • J.A. Eldred et al.

    The lens as a model for fibrotic disease

    Philos. Trans. R. Soc. Lond. B Biol. Sci.

    (2011)
  • P.D. Gupta et al.

    Causative and preventive action of calcium in cataracto-genesis

    Acta Pharmacol. Sin.

    (2004)
  • H.J. Hocker et al.

    Andrographolide derivatives inhibit guanine nucleotide exchange and abrogate oncogenic Ras function

    Proc. Natl. Acad. Sci. U. S. A.

    (2013)
  • K. Johar et al.

    Anterior capsular plaque in congenital cataract: occurrence, morphology, immunofluorescence, and ultrastructure

    Investig. Ophthalmol. Vis. Sci.

    (2007)
  • R.A. Kumar et al.

    Anticancer and immunostimulatory compounds from Andrographis paniculata

    J. Ethnopharmacol.

    (2004)
  • S. Kumar et al.

    Andrographolide inhibits osteopontin expression and breast tumor growth through down regulation of PI3 kinase/Akt signaling pathway

    Curr. Mol. Med.

    (2012)
  • M.T. Lau et al.

    Fibroblast growth factor 2 induces E-cadherin down-regulation via PI3K/Akt/mTOR and MAPK/ERK signaling in ovarian cancer cells

    PLoS One

    (2013)
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