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Steroidal dimer by001 inhibits proliferation and migration of esophageal cancer cells via multiple mechanisms

Cancer Chemotherapy and Pharmacology volume 83, pages 179–189 (2019)Cite this article

Abstract

Objective

To investigate the potential inhibitory effects of structurally novel steroidal dimer by001 in esophageal cancer in vitro.

Methods

The cytotoxicity of by001 on esophageal, gastric, neuroblastoma and prostate cancer cells was examined MTT assay and colony formation assay. By001 induced apoptosis and production of intracellular reactive oxygen species on esophageal cancer cells Ec109, TE-1 and human normal gastric epithelial cells GES-1 was detected by flow cytometry. The effect of by001 on mitochondrial membrane potential was detected by fluorescence microscope through JC-1 staining. The level of intracellular reactive oxygen species was measured by fluorescence microscope and flow cytometry via DCFH-DA staining. The effect of by001 on members of Bcl-2 family, Fas, LC3, PARP and caspases was determined by Western blot. The effect of by001 on migration was measured by

transwell assay.

Results

By001 effectively inhibited proliferation of esophageal, gastric, neuroblastoma and prostate cancer cells in a time- and concentration-dependent manner in vitro. By001 reduced the number and the size of colonies at low micromolar concentrations, elevated cellular ROS levels and caused mitochondrial dysfunction in esophageal cancer cells. Molecular mechanistic studies showed that by001 triggered apoptosis through regulating members of Bcl-2 family and Fas.

Conclusions

These findings suggested that by001 may inhibited proliferation of esophageal cancer cells through mitochondria and death receptor-mediated apoptotic pathways, autophagy induction, as well as suppressed migration of esophageal cancer cells.

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Funding

This study was supported by the Natural Science Foundation of China (Grant number 81472714) and the Key Medical Technologies Research and Development Program of Henan Provence (Grant number 201502027).

Author information

Author notes

  1. Sai-Qi Wang and Kai-Rui Zhou have contributed equally to this work.

Affiliations

  1. Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, No. 127, Dongming Road, Zhengzhou, 450008, China

    Sai-Qi Wang, Hui-Fang Lv, Liang-Yu Bie & Xiao-Bing Chen

  2. School of Pharmaceutical Sciences and Collaborative Innovation Center of New Drug Research and Safety Evaluation, Key Laboratory of Henan Province for Drug Quality and Evaluation, Zhengzhou University, Zhengzhou, 450001, China

    Kai-Rui Zhou

  3. Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, 266033, China

    Xiao-Li Shi

  4. Department of General Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, 450008, China

    Wei-Jie Zhao

Authors
  1. Sai-Qi Wang
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  2. Kai-Rui Zhou
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Corresponding author

Correspondence to Xiao-Bing Chen.

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Conflict of interest

Author Sai-Qi Wang declares that she has no conflict of interest. Author Kai-Rui Zhou declares that she has no conflict of interest. Author Xiao-Li Shi declares that she has no conflict of interest. Author Hui-Fang Lv declares that she has no conflict of interest. Author Liang-Yu Bie declares that he has no conflict of interest. Author Wei-Jie Zhao declares that he has no conflict of interest. Author Xiao-Bing Chen declares that he has no conflict of interest.

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Cite this article

Wang, SQ., Zhou, KR., Shi, XL. et al. Steroidal dimer by001 inhibits proliferation and migration of esophageal cancer cells via multiple mechanisms. Cancer Chemother Pharmacol 83, 179–189 (2019). https://doi.org/10.1007/s00280-018-3715-4

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  • DOI: https://doi.org/10.1007/s00280-018-3715-4

Keywords

  • Steroidal dimer
  • Steroidal N-heterocycles
  • Anti-proliferative activity
  • Migration
  • Esophageal cancer