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Title: 3,3'-diindolylmethane downregulates cyclin D1 through triggering endoplasmic reticulum stress in colorectal cancer cells
Authors: Xiaobo Zhang
Pakin Sukamporn
Shiqiang Zhang
Kyung Won Min
Seung Joon Baek
China Pharmaceutical University
Mahidol University
Shanghai TCM-Integrated Hospital
Medical University of South Carolina
Seoul National University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Jan-2017
Citation: Oncology Reports. Vol.38, No.1 (2017), 569-574
Abstract: As a major in vivo condensation product of indole-3-carbinol, which is mostly present in cruciferous vegetables, 3,3'-diindolylmethane (DIM) has been previously reported with anti-proliferative action in different types of cancer by our group and others. To further elucidate these underlying mechanisms, we examined the effect of DIM on cyclin D1, which was aberrantly overexpressed in various cancer cells and tumors. Herein, we found that DIM downregulated cyclin D1 expression in colorectal cancer cells (CRC), which was independent of PPAR-expression and protease activity. Furthermore, DIM did not affect cyclin D1 mRNA expression, suggesting DIM modulated cyclin D1 expression at the translational level. Subsequently, blocking eIF2-phosphorylation resulted from endoplasmic reticulum (ER) stress restored cyclin D1 in the presence of DIM. Thus, the present study demonstrates that DIM downregulates cyclin D1 through triggering ER stress in human colorectal cancer cells.
ISSN: 17912431
Appears in Collections:Scopus 2016-2017

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