Role of Sp in the Regulation of Notch1 Gene Expression by Curcumin

Abstract

Curcumin has diverse anticancer activities that lead to tumor growth inhibition of cancer cells and induction of apoptosis. Curcumin is involved in the regulation of multiple genes via transcription factors including NF-kB, STATs, AP1, and SP. Notch signaling plays critical roles in maintaining the balance between cell proliferation, differentiation and apoptosis, and thereby may contribute to the development of various cancers involving breast cancer. This study was to investigate the effects of curcumin on Notch1 gene expression and to explore the underlying mechanism. Here, we found that curcumin decreased the levels of Notch1 mRNA and protein in MDA-MB-231 human breast cancer cells, along with the downregulation of Sp family genes (Sp1, Sp2, Sp3, and Sp4). The repressive effect of curcumin on Notch1 gene transcription was confirmed by performing Notch1 promoter-driven reporter assay and three Sp-binding sites were identified on Notch1 promoter that may act as curcumin-respose elements. Moreover, treatment with mitramycin A, a specific Sp inhibitor, decreased the levels of Notch1 mRNA and protein in human breast cancer cells. Taken together, our results indicate that Notch1 gene expression is downregulated by curcumin, at least in part, through the suppression of Sp family, which may lead to apoptosis in human breast cancer cells.

Biocompatible, pH-sensitive AB2 miktoarm polymer-based polymersomes: preparation, characterization, and acidic pH-activated nanostructural transformation

“…, 5.8 kDa of polyHis) in mPEG- b -(polyHis) 2 represent 5.65 µmol/mg compared with 6.22 µmol/mg of polyHis 3.1kDa in mPEG 2kDa - b -polyHis 3.1kDa . 36 This result supports our previous findings that the proton buffering capacity of polyHis decreases as the molecular weight of polyHis increases. 36 …”

“…36 This result supports our previous findings that the proton buffering capacity of polyHis decreases as the molecular weight of polyHis increases. 36 …”

“…When estimating the buffering power of mPEG- b -(polyHis) 2 (namely, mPEG 2kDa - b -(polyHis 2.9kDa ) 2 when considering the molecular weights of each block) per unit mass within pH 4–7.4, the proton buffering capacity was found to be 4.2 µmol/mg compared with 3.78 µmol/mg for mPEG 2kDa - b -polyHis 3.1kDa . 36 The histidine-based 3-miktoarm copolymer showed a slightly better proton buffering capacity than the histidine-based diblock copolymer. Considering the weight fractions of the buffering blocks (here, polyHis) in the block copolymers, the two polyHis 2.9kDa blocks ( i.e.…”