CArG-driven GADD45alpha activated by resveratrol inhibits lung cancer cells.

CArG-driven GADD45alpha activated by resveratrol inhibits lung cancer cells.

Shi Qiwen; Geldenhuys Werner; Sutariya Vijaykumar; Bishayee Anupam; Patel Isha; Bhatia Deepak

Genes & cancer

2015

2015-05

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 GADD45alpha. In A549 lung cancer cells, endogenous GADD45alpha was not induced upon resveratrol treatment. Therefore, induction of exogenous GADD45alpha 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 GADD45alpha 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 GADD45alpha upon resveratrol treatment. Further analysis confirmed that both synthetic promoter and natural Egr-1 promoter were able to "turn on" the expression of GADD45alpha when combined with resveratrol, and subsequently led to suppression of cell proliferation and apoptosis.

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

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

220–230

5

6