Curcumin regulates miR-21 expression and inhibits invasion and metastasis in colorectal cancer

Abstract

A c c e p t e d M a n u s c r i p tLicenced copy. Copying is not permitted, except with prior permission and as allowed by law. © 2010 The Authors Journal compilation © 2010 Portland Press Limited AbstractCurcumin has promising potential in cancer prevention and therapy by interacting with proteins and modifying their expression and activity, which includes transcription factors, inflammatory cytokines, and factors of cell survival, proliferation, and angiogenesis. miR-21 is overexpressed in many tumors, promoting progression and metastasis. In the present study, we examined the potential of curcumin to regulate miR-21, tumor growth, invasion, and in vivo metastasis in colorectal cancer. In Rko and HCT116 cells, we identified two new transcriptional start sites of the miR-21 gene and delineated its promoter region. PMA stimulation induced miR-21 expression via motifs bound with AP-1 transcription factors. Curcumin treatment reduced miR-21 promoter activity and expression in a dose-dependent manner by inhibiting AP-1 binding to the promoter, and induced expression of tumor suppressor Pdcd4, which is a target of miR-21. Curcumin treated Rko and HCT116 cells were arrested in the G2/M phase with increasing concentrations. Furthermore, curcumin inhibited tumor growth, invasion and in vivo metastasis in the chicken-embryo-metastasis assay (CAM). Additionally, curcumin significantly inhibited miR-21 expression in primary tumors generated in vivo in the CAM assay by Rko and HCT116 cells (p<0.00006; p<0.035 respectively). Taken together, this is the first report to show that curcumin inhibits the transcriptional regulation of miR-21 via AP-1, suppresses cell proliferation, tumor growth, invasion, and in vivo metastasis, and stabilizes expression of tumor suppressor Pdcd4 in colorectal cancer.

Curcumin Effect on the Expressional Profile of OCT4, Nanog and Nucleostemin Genes in AGS (Adenocarcinoma) Cancer Cell Line

“…Curcumin is the release of cytochrome c and stability of P53 [23]. Curcumin inhibits the transcriptional network in stages and thus prevents the cell proliferation [26]. In another study of cell cycle arrest and growth of curcumin on gastric cancer cells was observed [27].…”

Induction of MicroRNA-9 Mediates Cytotoxicity of Curcumin Against SKOV3 Ovarian Cancer Cells

“…It has been reported that miR-186* is involved in curcumin-induced apoptosis in A549/ DDP multidrug-resistant human lung adenocarcinoma cells (Zhang et al, 2010). Downregulation of miR-21 transcription via activator protein 1 mediates the suppressive effects of curcumin on tumor growth, invasion and in vivo metastasis in colorectal cancer (Mudduluru et al, 2011). Induction of tumor suppressive miRNAs is another mechanism linked to the cytotoxicity of curcumin against cancer cells.…”

Curcumin Inhibits Cell Proliferation of Human Colorectal HCT116 Cells through Up-Regulation of Activating Transcription Factor 3 (ATF3)

“…구강암 세포주에서는 curcumin이 notch-1과 NF-kB 신호 전달체계를 억제시킴으로써, 암세포의 성장을 저해하고 세포 사멸을 유도하는 것으로 보고 되었다 [10]. 또한, 대장암 세포주 모델에서는curcumin이 miR-21의 발현을 조절함으로써, 암세 포의 성장과 전이과정을 저해하는 것으로 보고되었다 [11]. 그 러나, 대장암 HCT116 (Fig.…”