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OSW-1 inhibits tumor growth and metastasis by NFATc2 on triple-negative breast cancer.

Abstract
OSW-1 is a natural compound extracted from the bulbs of Ornithogalum saundersiae in 1992. It has been shown strong antitumor activities in various cancer cells. However, the effects of OSW-1 on tumor growth and metastasis in breast cancer are still poorly understood. In our research, we showed that OSW-1 had a strong anticancer effect on breast cancer cells, but lower toxicity to normal cells. Accordingly, it also revealed significant inhibition of tumor growth by OSW-1 in xenograft model. In addition, we performed Annexin V/PI-labeled flow cytometric assay and TUNEL assay and showed that OSW-1 inhibited tumor growth by inducing apoptosis. Furthermore, we carried out transwell assays and found that OSW-1 significantly repressed the migratory and invasive capabilities of triple-negative breast cancer (TNBC) cells via mediating epithelial-mesenchymal transition. Besides, OSW-1 also could inhibit metastasis in an orthotopic model and resulted in a longer survival compared with control group. Finally, we performed RNA-sequencing and cellular functions to investigate the molecular mechanism of how OSW-1 inhibits TNBC, and identified NFATc2 may as a pivotal factor for OSW-1-mediated effects on cell death, tumor growth, invasion, and migration.
AuthorsXiaorong Ding, Yumei Li, Jun Li, Yongmei Yin
JournalCancer medicine (Cancer Med) Vol. 9 Issue 15 Pg. 5558-5569 (08 2020) ISSN: 2045-7634 [Electronic] United States
PMID32515123 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Chemical References
  • Cholestenones
  • NFATC Transcription Factors
  • NFATC2 protein, human
  • Saponins
  • OSW 1
Topics
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Cholestenones (pharmacology)
  • Disease Models, Animal
  • Female
  • Humans
  • Mice
  • Mice, SCID
  • NFATC Transcription Factors (antagonists & inhibitors, metabolism)
  • Neoplasm Metastasis
  • Ornithogalum (chemistry)
  • Saponins (pharmacology)
  • Triple Negative Breast Neoplasms (drug therapy)

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