Format

Send to

Choose Destination
Genes Cancer. 2015 May;6(5-6):220-30.

CArG-driven GADD45α activated by resveratrol inhibits lung cancer cells.

Author information

1
Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, USA ; School of Biomedical Sciences, Kent State University, Kent, Ohio, USA.
2
Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, USA.
3
Department of Pharmaceutical Sciences, University of South Florida, Tampa, Florida, USA.
4
Department of Pharmaceutical Sciences, Larkin Health Sciences Institute College of Pharmacy, Miami, Florida, USA.
5
Bernard J. Dunn School of Pharmacy, Shenandoah University, Ashburn, Virginia, USA.

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.

KEYWORDS:

CArG elements; Egr-1; GADD45a; gene therapy; resveratrol; synthetic promoters

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center