Demethylwedelolactone derivatives inhibit invasive growth in vitro and lung metastasis of MDA-MB-231 breast cancer cells in nude mice

The anticancer properties of demethylwedelolactone (DWEL) and wedelolactone (WEL), which are naturally occurring coumestans, have not been well characterized. In this study, we investigated the anti-invasive effects of synthetic WEL and DWEL on human MDA-MB-231 breast cancer cells. We found that WEL and DWEL inhibited the anchorage-independent growth and also suppressed cell motility and cell invasion of MDA-MB-231 cells. In addition, WEL and DWEL reduced the activity and expression of matrix metalloproteinases (MMPs) involved in blocking the IκB-α/NFκB and MEK/ERK signaling pathways in MDA-MB-231 cells. Furthermore, DWEL suppressed the metastasis and lung colonization of the tumor cells in the nude mice. Altogether, these data suggest that DWEL derivatives exert anti-invasive growth effect on breast cancer cells.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► WEL and DWEL inhibit anchorage-independent growth in MDA-MB-231 breast cancer cells. ► WEL and DWEL repress cell motility and actin reorganization in MDA-MB-231 cells. ► WEL and DWEL suppress cell invasion in MDA-MB-231 cells. ► WEL and DWEL decrease phosphorylation of FAK, ERK, and IκB-α. ► DWEL inhibits lung colonization of MDA-MB-231 cells in nude mice.