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Identification of curcuminoid analogs that down‐regulate expression of the early growth response protein 1 in prostate cancer cells
Author(s) -
Aguiniga Lizath Monserrath,
Moreno America Yajaira,
Bisoffi Marco
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb204
Subject(s) - prostate cancer , curcuminoid , cancer research , curcumin , transcription factor , carcinogenesis , biology , cancer , flow cytometry , chemistry , microbiology and biotechnology , pharmacology , gene , biochemistry , genetics
The incidence of prostate cancer for US men is 1/6. It is important to identify therapeutic agents for chemoprevention. Our studies on histologically normal tumor adjacent human prostate tissues indicate an up‐regulation of transcription factor early growth response protein 1 (EGR‐1). We hypothesize that EGR‐1 mediates tumorigenesis and is a therapeutic target for chemoprevention. We aim to identify small molecule inhibitors with safe pharmacological profiles that can down‐regulate EGR‐1 expression in prostate cancer cells. We developed an EGR‐1 specific reporter system amenable to high‐throughput flow cytometric screening of small molecule libraries with combichemical design, including analogs of the natural product curcumin. We cloned a 522 bp EGR‐1 promoter fragment into a plasmid to regulate expression of green fluorescent protein (GFP) in transient transfections. Sequence analysis revealed recognition sites for several transcription factors. We report: (i) EGR‐1 specific GFP activation by mitogenic stimuli by fluorescence microscopy and flow cytometry; (ii) the inhibition of EGR‐1 promoter activation by curcuminoid compounds. We conclude that our reporter system is an ideal tool to identify and test therapeutic agents with chemopreventive potential for the risk of developing prostate cancer. This work is supported by NIH Grant RR0164880 and DOD PCRP Grant W81XWH‐07‐1‐0081.