Abstract
Activator protein-1 (AP1) is a transcription factor that consists of the Jun and Fos family proteins. It regulates gene expression in response to a variety of stimuli and controls cellular processes including proliferation, transformation, inflammation, and innate immune responses. AP1 binds specifically to 12-O-tetradecanoylphorbol-13-acetate (TPA) responsive element 5′-TGAG/CTCA-3′ (AP1 site). It has been found constitutively active in breast, ovarian, cervical, and lung cancers. Numerous studies have shown that inhibition of AP1 could be a promising strategy for cancer therapeutic applications. The present in silico study provides insights into the inhibition of Jun-Fos-DNA complex formation by curcumin derivatives. These derivatives interact with the amino acid residues like Arg155 and Arg158 which play a key role in binding of Jun-Fos complex to DNA (AP1 site). Ala151, Ala275, Leu283, and Ile286 were the residues present at binding site which could contribute to hydrophobic contacts with inhibitor molecules. Curcumin sulphate was predicted to be the most potent inhibitor amongst all the natural curcumin derivatives docked.
Highlights
Activator protein-1 (AP1) is a transcription factor that consists of either homo- or heterodimers of the Jun and Fos family proteins [1]
Numerous studies have shown that inhibition of AP1 has a profound effect on the behavior of cancer cells and tumors suggesting that AP1 could be a promising target for cancer therapy [10]
In the present study we investigate the interaction of curcumin derivatives with Jun-Fos complex by molecular docking studies
Summary
Activator protein-1 (AP1) is a transcription factor that consists of either homo- or heterodimers of the Jun and Fos family proteins [1]. Curcumin suppresses constitutive AP1 activity in HL-60, Raji, and prostate cancer cell lines (LNCaP, PC3, and DU145) [21,22,23,24,25]. Curcumin was reported to suppress LPS-induced cyclooxygenase-2 gene expression by inhibiting AP1 DNA binding in BV2 microglial cells [26]. It was confirmed that curcumin directly interacts with JunFos dimer and inhibits its binding to DNA (AP1 site) [27]. In the present study we investigate the interaction of curcumin derivatives with Jun-Fos complex by molecular docking studies
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