During the course of our search for bioactive metabolites from the marine sponges collected from Korean waters, 10 linear furanosesterterpenes characterized by a furan group and a terminal tetronic acid moiety were identified from Psammocinia sp. (order Dictyoceratida). An inseparable 1:1 mixture of (8E,13Z,20Z)-strobilinin and (7E,13Z,20Z)-felixinin (abbreviated as EZZ) was found to deliver significant cytotoxicity against some human solid tumor cell lines. Therefore, we carried out a study mainly focused on the mechanism of EZZ-induced cytotoxicity. In addition, as a part of our growing interest to screen dual anticancer and antioxidant drugs and inspired by the multi-double bonds in the structure of EZZ, the antioxidant activity of it was also evaluated.In my study, human cervical HeLa cells treated with EZZ showed significant decreases in its proliferation rate and viability (IC50 about 50 μM), which was associated with evidence of apoptosis. Nuclear changes observed under fluorescence microscope confirmed apoptosis occurrence and showed a typical pattern of chromatin condensation, which was further proved by DNA fragmentation by gel analysis. Furthermore, Annexin V-FITC/PI dual staining demonstrated that early apoptosis has occurred mainly at 24 h, which then progressed to late apoptosis after further treatment. In addition, the cell cycle was characterized by an arrest at S phase indicating EZZ might affect DNA replication or interfere in certain signal transduction pathway.It is well known that DNA replication in S phase is a strictly regulated event. Any stress exerting on this progress would lead to cell cycle arrest or apoptosis. The inhibitory effect of EZZ on DNA replication was proved both in [~3H]dTTP incorporation assay and in SV40 DNA in vitro replication system. In order to find the molecule target (or targets) of EZZ, we further checked the effects of EZZ on three important replication proteins: topo I, DNA pol α-primase and RPA. It was found that EZZ could significantly inhibit the DNA relaxation activity of topo I and this inhibition reached to 80% at 40 μM of EZZ. In addition, more than 70% of DNA pol α-primase activity was reduced by 20 μM of EZZ, while the ssDNA binding activity of RPA was slightly affected by 50 μM of EZZ. Herein, we suggest that EZZ-induced