Curcumin inhibits proliferation of breast cancer cells through Nrf2-mediated down-regulation of Fen1 expression.
Curcumin can inhibit cell proliferation of breast cancer, but the mechanism for this inhibition remains unclear. Over-expression of Flap endonuclease 1 (Fen1), a DNA repair-specific nuclease, is involved in the development of breast cancer. Nrf2 is a master regulator of cellular antioxidant defense systems. Curcumin can induce the expression of Nrf2 in both non-breast cancer cells and breast cancer cells. However, whether curcumin-induced inhibition of breast cancer cell proliferation may involve Nrf2-mediated Fen1 expression is not yet understood. In this study, we demonstrated that curcumin inhibited Fen1-dependent proliferation of MCF-7 cells and significantly induced Nrf2 protein expression while inhibiting Fen1 protein expression. Curcumin could down-regulate Fen1 gene expression in a Nrf2-dependent manner. Further investigation revealed that curcumin could lead to Nrf2 translocation from the cytoplasm to the nucleus and decrease Fen1 promoter activity by decreasing the recruitment of Nrf2 to the Fen1 promoter. These data suggest that curcumin may inhibit the proliferation of breast cancer cells through Nrf2-mediated down-regulation of Fen1 expression, which may be a new mechanism of curcumin-induced tumor growth inhibition.
Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China.
Bin
B
Chen
Department of Integrative Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Youzhi
Y
Zhang
Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China.
Yang
Y
Wang
Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China.
Jun
J
Rao
Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China.
Xiaomei
X
Jiang
Department of Integrative Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: zihuixu@yeah.net.
Zihui
Z
Xu
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D047369:Chromatin Immunoprecipitation; D003474:Curcumin / Q000494:pharmacology*; D015536:Down-Regulation; D005260:Female; D045585:Flap Endonucleases / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D034741:RNA, Small Interfering; D045585:Flap Endonucleases; C468317:FEN1 protein, human; D003474:Curcumin
Breast cancer; Curcumin; Fen1; Nrf2