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Cancer Chemotherapy and Pharmacology

, Volume 83, Issue 1, pp 179–189 | Cite as

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

  • Sai-Qi Wang
  • Kai-Rui Zhou
  • Xiao-Li Shi
  • Hui-Fang Lv
  • Liang-Yu Bie
  • Wei-Jie Zhao
  • Xiao-Bing ChenEmail author
Original Article
  • 75 Downloads

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.

Keywords

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

Notes

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).

Compliance with ethical standards

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.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhouChina
  2. 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 EvaluationZhengzhou UniversityZhengzhouChina
  3. 3.Department of PharmacyThe Affiliated Hospital of Qingdao UniversityQingdaoChina
  4. 4.Department of General SurgeryThe Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer HospitalZhengzhouChina

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