Two sesquiterpenoids, mansonone E (ME) and mansonone F (MF) were first isolated from the dried root bark of Ulmus pumila (shironire in Japanese), and their antiproliferative activities on human tumor cells were evaluated in vitro. ME had more potent cytotoxic effects on four tumor cell lines, human cervical cancer HeLa, human malignant melanoma A375-S2, human breast cancer MCF-7, and human histiocytic lymphoma U937, than those of MF. The results showed that ME induced oligonucleosomal fragmentation of DNA in HeLa cells and activated caspase-3, followed by the degradation of the inhibitor of caspase-activated DNase, decreased the expression of anti-apoptotic mitochondrial proteins Bcl-2 and Bcl-(XL), and increased that of proapoptotic Bax.