Resveratrol activated Egr-1 biosynthesis via ERK/JNK-Elk-1 signaling pathway in A549 cells. - GreenMedInfo Summary
CArG-driven GADD45α activated by resveratrol inhibits lung cancer cells.
Genes Cancer. 2015 May ;6(5-6):220-30. PMID: 26124921
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. Furtheranalysis 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.