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

• Published in: Korean Society for Biotechnology and Bioengineering Journal Vol. 28; no. 1
• Main Authors: Park, S.Y., Pusan National University, Pusan, Republic of Korea, Kang, Y.G., Pusan National University, Pusan, Republic of Korea, Bae, Y.H., Pusan National University, Pusan, Republic of Korea, Kim, S.R., Pusan National University, Pusan, Republic of Korea, Park, H.J., Pusan National University, Pusan, Republic of Korea, Kang, Y.S., Pusan National University, Pusan, Republic of Korea, Kim, M.K., Pusan National University, Pusan, Republic of Korea, Wee, H.J., Seoul National University, Seoul, Republic of Korea, Jang, H.O., Pusan National University, Pusan, Republic of Korea, Bae, M.K., Pusan National University, Pusan, Republic of Korea, Woo, J.S., Pusan National University, Pusan, Republic of Korea, Bae, S.K. (Pusan National University, Pusan, Republic of Korea)
• Format: Journal Article
• Language: Korean
• Published: 01.01.2013
• Subjects: breast cancer, Notch, Sp, MDA-MB-231; CURCUMA LONGA; DYES; TEINTURE; TINTES
• ISSN: 1225-7117

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 enes 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. 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 curmin, at least in part, through the suppression of Sp family, which may lead to apoptosis in human breast cancer cells.