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박선영(Seon-Yeong Park),강용규(Yong-Gyu Kang),배윤희(Yun-Hee Bae),김수륜(Su-Ryun Kim),박현주(Hyun-Joo Park),강영순(Young-Soon Kang),김미경(Mi-Kyoung Kim),위희준(Hee-Jun Wee),장혜옥(Hye-Ock Jang),배문경(Moon-Kyoung Bae),우재석(Jae Suk 한국생물공학회 2013 KSBB Journal Vol.28 No.1
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.