Targeting SP1 Transcription Factor in Prostate Cancer Therapy

Umesh      T. Sankpal; Steven      Goodison; Maen      Abdelrahim; Riyaz      Basha

doi:10.2174/157340611796799203

Abstract

Transcription factors are proteins that regulate gene expression by binding to specific DNA sequences within gene promoter regions. Specificity protein (Sp) family transcription factors play a critical role in various cellular processes and have been shown to be associated with tumorigenesis. The Sp family consists of several members that contain a highly conserved DNA-binding domain composed of three zinc fingers at the C-terminus and serine/threonine- and glutamine- rich transactivation domains at the N-terminal. Sp1 is elevated in several malignancies including prostate cancer and is associated with the prognosis of patients. Sp1, Sp3, and Sp4 regulate a variety of cancer associated genes that are involved in cell cycle, proliferation, cell differentiation, and apoptosis. Studies have shown that in prostate cancer, Sp1 regulates important genes like androgen receptor, TGF-β, c-Met, fatty acid synthase, matrix metalloprotein (MT1-MMP), PSA, and α-integrin. These results highlight the importance of Sp1 in prostate cancer and emphasize the potential therapeutic value of targeting Sp1. Several strategies, including the use of natural and synthetic compounds, have been used to inhibit Sp1 in prostate cancer. These include polyphenol quercetin, betulinic acid, acetyl-11-keto-beta-boswellic acid, tea phenols, isothiocyanates, thiazolidinediones, arsenic trioxide, and selenium. This review will describe the association of Sp1 in prostate cancer with a special emphasis on some of the agents tested to target Sp1 for the treatment of this malignancy.

Keywords: Cancer therapy, prostate cancer, PSA, Sp transcription factors, proteins, gene expression, gene promoter regions, Specificity protein, polyphenol quercetin, betulinic acid, acetyl-11-keto-beta-boswellic acid, thiazolidinediones, isothiocyanates, arsenic trioxide