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

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.

Keywords: NFATc2; OSW-1; apoptosis; epithelial-mesenchymal transition; metastasis; triple-negative breast cancer.