EM-12, a natural sesquiterpene lactone extracted from Elephantopus mollis, promotes cancer cell apoptosis by activating ER stress.

The Elephantopus mollis H.B.K. contains various sesquiterpene lactones that have shown anti-proliferative and proapoptotic effects in various cancers, although the underlying mechanisms are partially understood. Inducing of excessive ER stress is a potential cancer therapeutic strategy. However, ER stress activator remain limited in current clinical applications. In this study, we identified that EM-12, an uncovered sesquiterpene lactone isolated from Elephantopus mollis H.B.K., as a BiP ATPase activity inhibitor through BiP ATPase activity assay in vitro. This molecule also exhibits significantly greater cytotoxicity in numerous ovarian cancer cell lines, including paclitaxel-resistance ovarian cancer cell line, compared to transformed ovarian epithelial cell lines. In addition, EM-12 exerts broad-spectrum cytotoxicity against various human cancer cell lines, including liver, nasopharyngeal, and breast cancer cell lines. Mechanically, EM-12 promotes ER stress and ER-stress-related apoptosis to against cancer cells through inhibiting BiP ATPase activity.