Ethanolic extract of Euphorbia royleana Boiss. reduces metastasis of breast cancer cells and inhibits tumor progression in vivo

Metastasis is the most devastating attribute of breast cancer (BC) that leads to high mortality. It is a complex process of tumor cell migration, invasion, and angiogenesis. In this study, we evaluated the effect of ERA on BC metastasis and BC progression in vivo. The transwell invasion/migration and wound healing assays showed that ERA treatment significantly reduced the invasion and migration of BC cell lines. The expression of mesenchymal ( E-cadherin and N-cadherin ), matrix metalloproteinases ( MMP2, MMP9 ), and stemness markers ( Oct3) were down-regulated by ERA. Furthermore, ERA down-regulated angiogenic chemokines ( CXCL1/2/3, CXCL5, and CXCL12 ) expression in the highly metastatic MDA-MB-231 cell line. The clonogenic survival of BC cells was also reduced by ERA treatment. Strikingly, ERA prevented DMBA-induced tumor growth in Swiss albino mice as depicted by a high animal survival rate (84%) in the ERA group and histopathological analysis. Conclusively, this study revealed that ERA possesses anti-metastatic potential and also reduces the growth of BC in vivo. Moreover, the GC–MS data revealed the presence of biologically active compounds (Lupeol, Phytol, phytosterol) and some rare (9, 19-Cyclolanost) phyto metabolites in ERA extract. However, further studies are suggestive to identify and isolate the therapeutic agents from ERA to combat BC and metastasis.