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

• Published in: Cancer chemotherapy and pharmacology 2019-01, Vol.83 (1), p.179-189
• Main Authors: Wang, Sai-Qi, Zhou, Kai-Rui, Shi, Xiao-Li, Lv, Hui-Fang, Bie, Liang-Yu, Zhao, Wei-Jie, Chen, Xiao-Bing
• Format: Article
• Language: English
• Subjects: Apoptosis; Assaying; Autophagy; Bcl-2 protein; Cancer; Cancer Research; Cell proliferation; Colonies; Cytotoxicity; Dimers; Epithelial cells; Esophageal cancer; Esophagus; Flow cytometry; Fluorescence; In vitro methods and tests; Intracellular; Medicine; Medicine & Public Health; Membrane potential; Mitochondria; Neuroblastoma; Oncology; Original Article; Phagocytosis; Pharmacology/Toxicology; Poly(ADP-ribose) polymerase; Prostate cancer; Reactive oxygen species; Staining; Time dependence; Toxicity
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-018-3715-4

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.