Mechanism of cell cycle arrest by (8E,13Z,20Z)-strobilinin/(7E,13Z,20Z)-felixinin from a marine sponge Psammocinia sp.
Furanosesterterpenes, isolated from a marine sponge Psammocinia sp. have been reported to display significant cytotoxicity to some cancer cell lines. In this study, EZZ, an inseparable 1:1 mixture of (8E,3Z,20Z)-strobilinin and (7E,3Z,20Z)-felixinin, showed significant antiproliferative effect on human cervix carcinoma cell line (HeLa). Cell cycle analysis revealed that EZZ could arrest HeLa cells in S phase with a concomitant decrease in the cell population of G1 phase. By using simian virus (SV40) DNA in vitro replication system, we found that EZZ could inhibit DNA replication, which suggests that EZZ-induced S phase arrest might be the direct result of blocked DNA synthesis. Furthermore, low concentration of EZZ was found to be capable of significantly inhibiting the DNA cleavage by topoisomerase I (topo I) and reducing the polymerase alpha-primase (pol alpha-primase) activity, while the ssDNA binding activity of replication protein A (RPA) was less affected. Taken together, these results suggest that EZZ-induced cell cycle arrest in S phase correlate with the inhibition of DNA replication, and topo I and pol alpha-primase might be the two main target molecules.
Jiang
Yahong
Y
School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Ahn
Eun-Young
EY
Ryu
Seung-Hee
SH
Kim
Dong-Kyoo
DK
Park
Jang-Su
JS
Kang
Shin Won
SW
You
Song
S
Lee
Burm-Jong
BJ
Jung
Jee H
JH
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002384:Catalysis; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D004247:DNA / Q000378:metabolism; D019915:DNA Primase / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D011161:Porifera; D011485:Protein Binding; D051716:Replication Protein A / Q000378:metabolism; D016196:S Phase; D013539:Simian virus 40 / Q000235:genetics; D013729:Terpenes / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004277:DNA, Single-Stranded; D051716:Replication Protein A; D013729:Terpenes; C507438:felixinin; C507437:strobilinin; D004247:DNA; D019915:DNA Primase; D004264:DNA Topoisomerases, Type I