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KMID : 0380020130280010001
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Korean Journal of Biotechnology and Bioengineering
2013 Volume.28 No. 1 p.1 ~ p.6
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Role of Sp in the Regulation of Notch1 Gene Expression by Curcumin
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Park Seon-Yeong
Kang Yong-Gyu
Bae Yun-Hee
Kim Su-Ryun
Park Hyun-Joo
Kang Young-Soon
Kim Mi-Kyoung
Wee Hee-Jun
Jang Hye-Ock
Bae Moon-Kyoung
Woo Jae-Suk
Bae Soo-Kyung
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Abstract
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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-κB, 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.
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KEYWORD
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Notch, Sp, curcumin, breast cancer, MDA-MB-231
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