Document Type
Article
Publication Date
2015
Keywords
resveratrol, CArG elements, Egr-1, GADD45α, gene therapy, synthetic promoters
Digital Object Identifier (DOI)
https://doi.org/10.18632/genesandcancer.62
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.
Rights Information
This work is licensed under a Creative Commons Attribution 3.0 License.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Genes & Cancer, v. 6, issue 5-6, art. 62
Scholar Commons Citation
Shi, Qiwen; Geldenhuys, Werner; Sutariya, Vijaykumar; Bishayee, Anupam; Patel, Isha; and Bhatia, Deepak, "CArG-driven GADD45α Activated by Resveratrol Inhibits Lung Cancer Cells" (2015). Pharmacy Faculty Publications. 77.
https://digitalcommons.usf.edu/pharm_facpub/77
