3,3'-Diindolylmethane inhibits the proliferation of esophageal squamous cell carcinoma cells via downregulation of STIM1

Xiong,Chenyi; Tang,Yining; Li,Feng; Ye,Yang; Li,Xiaoran; Lin,Jinxing; Dai,Sunxian

doi:10.3892/ol.2024.14473

3,3'-Diindolylmethane inhibits the proliferation of esophageal squamous cell carcinoma cells via downregulation of STIM1

Authors:
- Chenyi Xiong
- Yining Tang
- Feng Li
- Yang Ye
- Xiaoran Li
- Jinxing Lin
- Sunxian Dai
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Affiliations: Department of Thoracic Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212000, P.R. China, Department of Preventive Medicine and Public Health Laboratory Science, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China, Cell Medicine Laboratory, School of Medicine, Soochow University, Soochow, Jiangsu 215000, P.R. China
Published online on: May 28, 2024 https://doi.org/10.3892/ol.2024.14473
Article Number: 339
Copyright: © Xiong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

3,3'-Diindolylmethane (DIM) is a natural phytochemical derived from cruciferous plants that has inhibitory effects on a wide range of tumor cells; however, its relevant effects on esophageal cancer cells have been poorly studied. Therefore, in the present study, a pharmacology network approach was used to predict the possible core targets of DIM acting on esophageal cancer. Subsequently, using in vitro experiments, TE-1 human esophageal cancer cells were treated with different concentrations of DIM (0, 40, 60 and 80 µM) for 24 h. Changes in cell activity were detected by Cell Counting Kit-8 assay, and changes in the expression levels of stromal interaction molecule 1 (STIM1) and apoptosis-related proteins, B-cell lymphoma-2 (Bcl-2) and Bax, were assessed by western blotting, followed by the upregulation of STIM1 by thapsigargin (Tg). Network pharmacology analysis showed that there were 39 potential core targets of DIM in esophageal cancer. The results of the in vitro experiments showed that DIM could inhibit the viability of esophageal cancer cells, downregulate the expression of STIM1 and Bcl-2 proteins and upregulate the expression of Bax protein, all in a concentration-dependent manner. The results also demonstrated that toxic carotenoids were agonist against STIM1 protein and upregulated STIM1 and Bax protein expression. After agonizing STIM1 protein expression using Tg, DIM was able to counteract the expression trend of STIM1, Bcl-2 and Bax protein in TE-1 cells. In summary, DIM induced apoptosis and inhibited the viability of esophageal cancer cells by downregulating the expression of STIM1 protein; therefore, the natural phytochemical, DIM, may be a potential substance for the early prevention and treatment of esophageal cancer cells.

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