title: CArG-driven GADD45α activated by resveratrol inhibits lung cancer cells.
abstract: We report anticarcinogenic effects of suicide gene therapy that relies on the use of resveratrol-responsive CArG elements from the Egr-1 promoter to induce GADD45α. In A549 lung cancer cells, endogenous GADD45α was not induced upon resveratrol treatment. Therefore, induction of exogenous GADD45α resulted in growth inhibition. Resveratrol transiently induced Egr-1 through ERK/JNK-ElK-1. Hence, we cloned natural or synthetic Egr-1 promoter upstream of GADD45α cDNA to create a suicide gene therapy vector. Since natural promoter may have antagonized effects, we tested synthetic promoter that contains either five, six or nine repeats of CArG elements essential in the Egr-1 promoter to drive the expression of GADD45α upon resveratrol treatment. Further analysis confirmed that both synthetic promoter and natural Egr-1 promoter were able to "turn on" the expression of GADD45α when combined with resveratrol, and subsequently led to suppression of cell proliferation and apoptosis.
authors.affiliation: Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, USA ; School of Biomedical Sciences, Kent State University, Kent, Ohio, USA.
authors.forename: Qiwen
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, USA.
authors.forename: Werner
authors.initials: W
authors.lastname: Geldenhuys
authors.affiliation: Department of Pharmaceutical Sciences, University of South Florida, Tampa, Florida, USA.
authors.forename: Vijaykumar
authors.initials: V
authors.lastname: Sutariya
authors.affiliation: Department of Pharmaceutical Sciences, Larkin Health Sciences Institute College of Pharmacy, Miami, Florida, USA.
authors.forename: Anupam
authors.initials: A
authors.lastname: Bishayee
authors.affiliation: Bernard J. Dunn School of Pharmacy, Shenandoah University, Ashburn, Virginia, USA.
authors.forename: Isha
authors.initials: I
authors.lastname: Patel
authors.affiliation: Bernard J. Dunn School of Pharmacy, Shenandoah University, Ashburn, Virginia, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Bhatia
keywords: CArG elements; Egr-1; GADD45a; gene therapy; resveratrol; synthetic promoters