3,3'-diindolylmethane downregulates cyclin D1 through triggering endoplasmic reticulum stress in colorectal cancer cells

Zhang,Xiaobo; Sukamporn,Pakin; Zhang,Shiqiang; Min,Kyung-Won; Baek,Seung  Joon

doi:10.3892/or.2017.5693

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
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Affiliations: Department of Basic Medical Science, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand, Oncology Department, Shanghai TCM-Integrated Hospital, Shanghai 200082, P.R. China, Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA, Laboratory of Signal Transduction, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Republic of Korea
Published online on: June 1, 2017 https://doi.org/10.3892/or.2017.5693
Pages: 569-574

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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 PPARγ 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 eIF2α 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.

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