Eupalinolide O, a novel sesquiterpene lactone from Eupatorium lindleyanum DC., induces cell cycle arrest and apoptosis in human MDA-MB-468 breast cancer cells.

Abstract

Sesquiterpene lactones have been confirmed to have potential antitumor activity. Here, we demonstrated that EupalinolideO(EO), a novel sesquiterpene lactone isolated from Eupatorium lindleyanum DC., showed significant anticancer activity against human MDA-MB-468 breast cancer cells. The cytotoxicity induced by EO was mediated by induction of apoptosis. Flow cytometric analysis demonstrated that EO treatment resulted in loss of the mitochondrial membrane potential in cancer cells which is regarded as a hallmark of apoptosis. Further study demonstrated that EO induced apoptotic cell death in the MDA-MB-468 cells through the activation of caspases. The effect of EO on the induction of apoptosis was significantly prevented by the treatment of pan-caspase inhibitor Z-VAD-FMK. We also found that EO treatment resulted in cell cycle arrest in the G2/M phase. The expression of cell cycle-related proteins (cyclin B1 and cdc2) was significantly decreased. Furthermore, the suppression of the Akt pathway in the MDA-MB-468 cells was observed. Collectively, EO suppressed the growth of the MDA-MB‑468 cells possibly by cell cycle arrest in the G2/M phase and the induction of caspase-dependent apoptosis. These results suggest that EO is a promising natural compound for breast cancer therapy.