Article Publish Status: FREE
Abstract Title:

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

Abstract Source:

Genes Cancer. 2015 May ;6(5-6):220-30. PMID: 26124921

Abstract Author(s):

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

Article Affiliation:

Qiwen Shi


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.

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