Steroidal dimer by001 inhibits proliferation and migration of esophageal cancer cells via multiple mechanisms
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To investigate the potential inhibitory effects of structurally novel steroidal dimer by001 in esophageal cancer in vitro.
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
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.
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.
KeywordsSteroidal dimer Steroidal N-heterocycles Anti-proliferative activity Migration Esophageal cancer
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.
This article does not contain any studies with human participants or animals performed by any of the authors.
- 5.Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J, Mulders PF, Basch E, Small EJ, Saad F, Schrijvers D, Van Poppel H, Mukherjee SD, Suttmann H, Gerritsen WR, Flaig TW, George DJ, Yu EY, Efstathiou E, Pantuck A, Winquist E, Higano CS, Taplin ME, Park Y, Kheoh T, Griffin T, Scher HI, Rathkopf DE (2013) Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368(2):138–148. https://doi.org/10.1056/NEJMoa1209096 CrossRefGoogle Scholar
- 7.Purushottamachar P, Godbole AM, Gediya LK, Martin MS, Vasaitis TS, Kwegyir-Afful AK, Ramalingam S, Ates-Alagoz Z, Njar VC (2013) Systematic structure modifications of multitarget prostate cancer drug candidate galeterone to produce novel androgen receptor down-regulating agents as an approach to treatment of advanced prostate cancer. J Med Chem 56(12):4880–4898. https://doi.org/10.1021/jm400048v CrossRefGoogle Scholar
- 22.Wang SQ, Wang C, Chang LM, Zhou KR, Wang JW, Ke Y, Yang DX, Shi HG, Wang R, Shi XL, Ma LY, Liu HM (2016) Geridonin and paclitaxel act synergistically to inhibit the proliferation of gastric cancer cells through ROS-mediated regulation of the PTEN/PI3K/Akt pathway. Oncotarget 7(45):72990–73002. https://doi.org/10.18632/oncotarget.12166 Google Scholar
- 23.Wang SQ, Wang C, Wang JW, Yang DX, Wang R, Wang CJ, Li HJ, Shi HG, Ke Y, Liu HM (2017) Geridonin, a novel derivative of oridonin, inhibits proliferation of MGC 803 cells both in vitro and in vivo through elevating the intracellular ROS. J Pharm Pharmacol 69(2):213–221. https://doi.org/10.1111/jphp.12678 CrossRefGoogle Scholar